A Phase 2 Study of Sitravatinib in Combination With PD-(L... | NCT03606174 | Trialant
NCT03606174
Sponsor
Mirati Therapeutics Inc.
Status
Terminated
Last Update Posted
Aug 24, 2023Actual
Enrollment
260Actual
Phase
Phase 2
Conditions
Urothelial Carcinoma
Urothelial Carcinoma Bladder
Urothelial Carcinoma Ureter
Urothelial Carcinoma of the Renal Pelvis and Ureter
Urothelial Carcinoma Urethra
Interventions
Sitravatinib
Nivolumab
Pembrolizumab
Enfortumab vedotin
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT03606174
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
516-003
Secondary IDs
Not provided
Brief Title
A Phase 2 Study of Sitravatinib in Combination With PD-(L)1 Checkpoint Inhibitor Regimens in Patients With Advanced or Metastatic Urothelial Carcinoma
Official Title
A Phase 2 Study of Sitravatinib in Combination With PD-(L)1 Checkpoint Inhibitor Regimens in Patients With Advanced or Metastatic Urothelial Carcinoma
Acronym
Not provided
Organization
Mirati Therapeutics Inc.INDUSTRY
Status Module
Record Verification Date
Aug 2023
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
The study was terminated due to sponsor decision / portfolio prioritization, and not due to safety reasons.
Expanded Access Info
No
Start Date
Sep 11, 2018Actual
Primary Completion Date
Aug 3, 2022Actual
Completion Date
Aug 22, 2022Actual
First Submitted Date
Jul 20, 2018
First Submission Date that Met QC Criteria
Jul 20, 2018
First Posted Date
Jul 30, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Aug 3, 2023
Results First Submitted that Met QC Criteria
Aug 3, 2023
Results First Posted Date
Aug 24, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Aug 3, 2023
Last Update Posted Date
Aug 24, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Mirati Therapeutics Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The study will evaluate the clinical activity of PD-(L)1 Checkpoint Inhibitor regimens in combination with the investigational agent sitravatinib in patients with advanced or metastatic urothelial carcinoma.
Detailed Description
Sitravatinib is an orally-available, small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR family, KIT, FLT3, Trk family, RET, DDR2 and selected Eph family members. Nivolumab is a human IgG monoclonal antibody that binds to the programmed cell death-1(PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response including anti-tumor immune response. Combining an immunotherapeutic PD-L1 checkpoint inhibitor with an agent that has both immune modulatory and antitumor properties could enhance the antitumor efficacy observed with either agent alone. Sitravatinib selectively inhibits key molecular and cellular pathways strongly implicated in checkpoint inhibitor resistance and therefore represents a rational strategy to enhance or restore anti-tumor immunity when combined with nivolumab, a checkpoint inhibitor therapy.
Pembrolizumab is a humanized IgG4 monoclonal antibody that binds to the PD-1 receptor and selectively blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. Enfortumab vedotin (enfortumab) is an investigational ADC that is comprised of a fully human anti-Nectin-4 IgG1 monoclonal antibody conjugated to MMAE via a protease-cleavable linker. Enfortumab binds to cells that express Nectin-4 with high affinity, triggering the internalization and release of MMAE in target cells, inducing cell cycle arrest and apoptotic cell death. Early efficacy results from enfortumab in combination with pembrolizumab in frontline cisplatin-ineligible urothelial carcinoma in the ongoing EV-103 study have demonstrated encouraging activity with a safety profile that appears manageable and tolerable. Addition of sitravatinib to this combination might further augment clinical activity by selectively inhibiting key molecular and cellular pathways strongly implicated in checkpoint inhibitor resistance.
Conditions Module
Conditions
Urothelial Carcinoma
Urothelial Carcinoma Bladder
Urothelial Carcinoma Ureter
Urothelial Carcinoma of the Renal Pelvis and Ureter
Urothelial Carcinoma Urethra
Keywords
MGCD516
Antineoplastic Agents
Immunologic Factors
Nivolumab
Tyrosine Kinase Inhibitor
VEGFR
TAM RTKs
PD-1
PD-L1
Pembrolizumab
Enfortumab vedotin
Checkpoint Inhibitors
Antibody Drug Conjugates
ADC
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
260Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1
Experimental
Patients previously treated with checkpoint inhibitor and platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Drug: Sitravatinib
Drug: Nivolumab
Cohort 2
Experimental
Patients previously treated with checkpoint inhibitor, but ineligible for platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Drug: Sitravatinib
Drug: Nivolumab
Cohort 3
Experimental
Patients previously treated with selected immunotherapies and platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Drug: Sitravatinib
Drug: Nivolumab
Cohort 4
Experimental
Patients previously treated with with selected immunotherapies, but ineligible for platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Drug: Sitravatinib
Drug: Nivolumab
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Sitravatinib
Drug
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Objective Response Rate (ORR)
ORR was defined as the number of participants documented to have a confirmed investigator-assessed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.
Up to approximately 3 years
Secondary Outcomes
Measure
Description
Time Frame
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any reaction, side effect or other undesirable medical event that occurred during participation in a clinical trial, regardless of treatment group or suspected causal relationship to study treatment. Any clinically significant changes from baseline in laboratory results were recorded as AEs.
Day 1 up to approximately 3 years
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Diagnosis of urothelial carcinoma
Adequate bone marrow and organ function
Exclusion Criteria:
Uncontrolled tumor in the brain
Unacceptable toxicity with prior checkpoint inhibitor
Impaired heart function
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Hirak Der-Torossian, MD
Mirati Therapeutics Inc.
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
The University of Arizona Cancer Center
Tucson
Arizona
85724
United States
University of California Irvine
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Screening tests and procedures were performed within the 28 days preceding administration of the first dose.
Recruitment Details
260 participants were enrolled into this study at investigative sites in the United States.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jun 22, 2020
Jul 31, 2023
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
There are 9 cohorts (having 9-55 maximum patients enrolled in each; based upon response rate). Patients are assigned to cohorts based upon their prior treatments for urothelial carcinoma.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Cohort 5
Experimental
Patients previously treated with platinum-based chemotherapy, but never treated with checkpoint inhibitor. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Drug: Sitravatinib
Drug: Nivolumab
Cohort 6
Experimental
Patients ineligible for treatment with platinum-based chemotherapy and never treated with checkpoint inhibitor. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Drug: Sitravatinib
Drug: Nivolumab
Cohort 7
Experimental
Patients previously treated with antibody-drug conjugate, checkpoint inhibitor and platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Drug: Sitravatinib
Drug: Nivolumab
Cohort 8
Experimental
Patients previously treated with antibody-drug conjugate and checkpoint inhibitor, but ineligible for platinum-based chemotherapy. Nivolumab over 30 min IV infusion (240 mg IV every 2 weeks or 480 mg every 4 weeks) and sitravatinib 120 mg orally once per day continuously in 28-day cycles.
Drug: Sitravatinib
Drug: Nivolumab
Cohort 9
Experimental
Patients previously treated with checkpoint inhibitor and platinum-based chemotherapy. There are 2 parts to this Cohort - a lead-in dose escalation portion and a dose expansion portion. In the dose escalation portion, treatment with up to 3 dose levels of sitravatinib in combination with up to 2 dose levels of pembrolizumab and enfortumab combination regimen to determine the recommended doses to be used in the combination treatment regimen and those doses will be further studied in the dose expansion portion. Pembrolizumab 200 mg over 30 min IV infusion every 3 weeks, sitravatinib orally once per day continuously in 21-day cycles (at 35 mg, 50 mg, 70 mg, or 100 mg) and enfortumab vedotin over 30 min IV infusion on Day 1 and Day 8 in 21-day cycles (at 1 mg/kg or 1.25 mg/kg).
Drug: Sitravatinib
Drug: Pembrolizumab
Drug: Enfortumab vedotin
Cohort 5
Cohort 6
Cohort 7
Cohort 8
Cohort 9
MGCD516
Nivolumab
Drug
Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Cohort 5
Cohort 6
Cohort 7
Cohort 8
Opdivo
Pembrolizumab
Drug
Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody
Cohort 9
Keytruda
Enfortumab vedotin
Drug
Enfortumab is a Nectin-4 directed antibody-drug conjugate (ADC) comprised of a monoclonal antibody conjugated to the small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE)
Cohort 9
Padcev
Number of Participants Who Experienced a Serious Adverse Event (SAE)
An SAE was defined as any event that resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/permanent damage (substantial disruption of the ability to conduct normal life functions), a congenital anomaly/birth defect, or may have jeopardized the participant and may have required medical or surgical intervention to prevent intensive treatment in an emergency room or at home (e.g. for allergic bronchospasm, blood dyscrasias or convulsions) that do not result in inpatient hospitalization, development of drug dependency or drug abuse.
Day 1 up to approximately 3 years
Number of Participants Who Experienced a Treatment-related Adverse Event
A treatment-related adverse event was defined as an adverse event determined to have a possible causal relationship to the study treatment(s) by the investigator. An adverse event was defined as any reaction, side effect or other undesirable medical event that occurred during participation in a clinical trial. Any clinically significant changes from baseline in laboratory results were recorded as adverse events.
Day 1 up to approximately 3 years
Duration of Response (DOR)
DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of objective progression of disease (PD) per RECIST V1.1, or to death due to any cause in the absence of documented PD. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare efficacy endpoints across Cohort 9 dose levels.
Up to approximately 3 years
Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR) was defined as the number of participants documented to have a confirmed CR, PR, or stable disease (SD), per RECIST V1.1, documented during at least 1 on-study assessment. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. SD was defined as target lesions increasing by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds.
Up to approximately 3 years
Progression-Free Survival (PFS)
PFS was defined as the time from date of first study treatment to first PD per RECIST V1.1, or death due to any cause in the absence of documented PD.
Up to approximately 3 years
1-Year Survival Rate
Survival was defined as the time from date of first study treatment to death due to any cause. Kaplan-Meier (product limit) estimates of the percentage of participants who died at 1-year was calculated to estimate the 1-year survival rate, defined as the percentage of participants alive at 1 year. Confidence Intervals were calculated based on Greenwood's formula. Participants who discontinued prior to 1-year were censored on the last date that they were known to be alive. For participants with no follow-up after first dose of study drug, survival rate was censored at the date of first dose (Day 1).
1 year
Overall Survival (OS)
OS was defined as the time from date of first study treatment to death due to any cause.
Up to approximately 3 years
Geometric Mean Blood Plasma Concentration of Sitravatinib
Blood draws for analysis of blood plasma concentrations of sitravatinib were collected following electrocardiograms and assessment of vital signs. Concentration data below the limit of quantification were set to 0.
Cohort 9 Lead-in Dose Escalation Part Only: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
A DLT was defined as any of the following events considered to be causally related to treatment with sitravatinib in combination with pembrolizumab and enfortumab in the lead-in dose escalation part of Cohort 9 (as pre-specified): hematological DLTs (Grade 4 neutropenia, thrombocytopenia, anemia unexplained by underlying disease, ≥Grade 3 febrile neutropenia or neutropenia with significant clinical sequelae, or any requirement for a platelet transfusion), non-hematological DLTs (≥Grade 4 infusion related reaction, non-hematological toxicity, Grade 3 infusion related reaction that does not resolve within 24 hours, hypertension that cannot be controlled with medical therapy), other Grade 3 non-hematologic toxicity lasting for >3 days, with exceptions, Grade 2 pneumonitis or colitis, ≥Grade 3 non-hematological laboratory abnormalities, alanine transaminase>3 x upper limit of normal (ULN) with bilirubin> 2xULN, and other related toxic effects may have been assessed as DLTs.
Cycle 1 Day 1 through pre-dose Cycle 2 Day 1 (cycle for Cohort 9 was 21 days)
Irvine
California
92868
United States
Rocky Mountain Cancer Centers
Aurora
Colorado
80012
United States
Yale School of Medicine
New Haven
Connecticut
06510
United States
SCRI - Florida Cancer Specialists- North Region
St. Petersburg
Florida
33705
United States
Moffitt Cancer Center
Tampa
Florida
33612
United States
SCRI - Florida Cancer Specialists - West Palm Beach
West Palm Beach
Florida
33401
United States
The University of Chicago
Chicago
Illinois
60637
United States
Indiana University - Melvin & Bren Simon Cancer Center
Indianapolis
Indiana
46202
United States
Norton Cancer Institute - Broadway
Louisville
Kentucky
40202
United States
Ochsner Cancer Institute
New Orleans
Louisiana
70121
United States
Maryland Oncology Hematology, P.A.
Lanham
Maryland
20706
United States
Dana Farber Cancer Institute
Boston
Massachusetts
02215
United States
Barbara Ann Karmanos Cancer Institute
Detroit
Michigan
48201
United States
Washington University School of Medicine - Siteman Cancer Center
St Louis
Missouri
63110
United States
GU Research Network/Urology Cancer Center
Omaha
Nebraska
68130
United States
Comprehensive Cancer Centers of Nevada - Southwest
Las Vegas
Nevada
89169
United States
New York Oncology Hematology - Albany Medical Center
Albany
New York
12206
United States
Roswell Park Cancer Institute
Buffalo
New York
14263
United States
Northwell Health Monter Cancer Center
Lake Success
New York
11042
United States
NYU Langone Laura & Isaac Perlmutter Cancer Center
New York
New York
10016
United States
Memorial Sloan-Kettering Cancer Center
New York
New York
10065
United States
New York-Presbyterian - Weill Cornell Medical Center
New York
New York
10065
United States
University of North Carolina - Lineberger Comprehensive Cancer Center
Chapel Hill
North Carolina
27599
United States
Duke University Hospital
Durham
North Carolina
27710
United States
The Ohio State University College of Medicine
Columbus
Ohio
43202
United States
Allegheny General Hospital
Pittsburgh
Pennsylvania
15212
United States
Vanderbilt University - Ingram Cancer Center
Nashville
Tennessee
37232
United States
Texas Oncology-Austin Central
Austin
Texas
78731
United States
Texas Oncology- Memorial City
Houston
Texas
77024
United States
University of Texas - MD Anderson Cancer Center
Houston
Texas
77030
United States
University of Texas Health Science Center
San Antonio
Texas
78229
United States
Texas Oncology - Tyler
Tyler
Texas
75702
United States
Virginia Cancer Specialists- Fairfax
Fairfax
Virginia
22031
United States
Virginia Oncology Associates
Norfolk
Virginia
23502
United States
Seattle Cancer Center Alliance
Seattle
Washington
98109
United States
FG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
FG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
FG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
FG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
FG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
FG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
FG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
FG008
Cohort 9 Dose Level 1
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 1 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.25 mg/kg IV infusion on Days 1 and 8 every 3 weeks (Q3W), and pembrolizumab 200 mg Q3W as an IV infusion.
FG009
Cohort 9 Dose Level 2
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 2 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
FG010
Cohort 9 Dose Level 3
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 3 were enrolled to receive sitravatinib 70 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
FG00049 subjects
FG00123 subjects
FG00218 subjects
FG0039 subjects
FG00453 subjects
FG00527 subjects
FG00656 subjects
FG0079 subjects
FG0088 subjects
FG0094 subjects
FG0104 subjects
Started Cohort 9 Lead-in Dose-escalation Part
FG0000 subjectsN/A for Cohorts 1-8
FG0010 subjectsN/A for Cohorts 1-8
FG0020 subjectsN/A for Cohorts 1-8
FG0030 subjectsN/A for Cohorts 1-8
FG0040 subjectsN/A for Cohorts 1-8
FG0050 subjectsN/A for Cohorts 1-8
FG0060 subjectsN/A for Cohorts 1-8
FG0070 subjectsN/A for Cohorts 1-8
FG0088 subjects
FG0094 subjects
FG0104 subjects
Started Cohort 9 Dose-expansion Part
FG0000 subjectsN/A for Cohorts 1-8
FG0010 subjectsN/A for Cohorts 1-8
FG0020 subjectsN/A for Cohorts 1-8
FG0030 subjectsN/A for Cohorts 1-8
FG0040 subjectsN/A for Cohorts 1-8
FG0050 subjectsN/A for Cohorts 1-8
FG0060 subjectsN/A for Cohorts 1-8
FG0070 subjectsN/A for Cohorts 1-8
FG0080 subjects
FG0090 subjects
FG0100 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
NOT COMPLETED
FG00049 subjects
FG00123 subjects
FG00218 subjects
FG0039 subjects
FG00453 subjects
FG00527 subjects
FG00656 subjects
FG0079 subjects
FG0088 subjects
FG0094 subjects
FG0104 subjects
Type
Comment
Reasons
Death
FG00037 subjects
FG00115 subjects
FG00215 subjects
FG0037 subjects
FG00435 subjects
FG00512 subjects
FG00635 subjects
FG0078 subjects
FG0085 subjects
FG0093 subjects
FG0100 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0006 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Study Terminated by Sponsor
FG0005 subjects
FG0017 subjects
FG0023 subjects
FG0030 subjects
FG004
Miscellaneous
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG004
Measured in the safety population, which included all participants who received ≥ 1 dose of any study treatment (sitravatinib, nivolumab, pembrolizumab, or enfortumab vedotin).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
BG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
BG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
BG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
BG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
BG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
BG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
BG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
BG008
Cohort 9 Dose Level 1
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 1 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.25 mg/kg IV infusion on Days 1 and 8 every 3 weeks (Q3W), and pembrolizumab 200 mg Q3W as an IV infusion.
BG009
Cohort 9 Dose Level 2
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 2 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
BG010
Cohort 9 Dose Level 3
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 3 were enrolled to receive sitravatinib 70 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
BG011
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00049
BG00123
BG00218
BG0039
BG00453
BG00527
BG00656
BG0079
BG0088
BG0094
BG0104
BG011260
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00067.3± 9.63
BG00172.3± 7.94
BG00267.6± 12.89
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00013
BG0017
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0004
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Objective Response Rate (ORR)
ORR was defined as the number of participants documented to have a confirmed investigator-assessed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.
Measured in the Full Analysis Set, which included participants who received ≥ 1 dose of each study treatment drug (ie, ≥ 1 dose of both sitravatinib and nivolumab for Cohorts 1 to 8, or ≥ 1 dose each of sitravatinib, pembrolizumab, and enfortumab vedotin for Cohort 9). Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare efficacy endpoints across Cohort 9 dose levels.
Posted
Count of Participants
Participants
Up to approximately 3 years
ID
Title
Description
OG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
OG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG008
Cohort 9
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants were enrolled to 3 dose levels of sitravatinib in combination with pembrolizumab and enfortumab vedotin. Sitravatinib was received orally via capsules QD in 21-day cycles at doses 35 mg and 70 mg. Pembrolizumab was received as an IV infusion over approximately 30 minutes (± 5 minutes) at 200 mg every 3 weeks (Q3W), in accordance with the current pembrolizumab USPI. Enfortumab vedotin dosing was based on participant weight, starting at 1.25 mg/kg up to 125 mg/kg QD, with a dose de-escalation step to 1 mg/kg. Enfortumab vedotin was received as an IV infusion over approximately 30 minutes (± 5 minutes) on Days 1 and 8 of a 21-day cycle.
Units
Counts
Participants
OG00049
OG00123
OG00218
OG003
Title
Denominators
Categories
Title
Measurements
OG0006
OG0015
OG0024
OG003
Secondary
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any reaction, side effect or other undesirable medical event that occurred during participation in a clinical trial, regardless of treatment group or suspected causal relationship to study treatment. Any clinically significant changes from baseline in laboratory results were recorded as AEs.
Measured in the safety population, which included all participants who received ≥ 1 dose of any study treatment (sitravatinib, nivolumab, pembrolizumab, or enfortumab vedotin).
Posted
Count of Participants
Participants
Day 1 up to approximately 3 years
ID
Title
Description
OG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
OG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
Secondary
Number of Participants Who Experienced a Serious Adverse Event (SAE)
An SAE was defined as any event that resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/permanent damage (substantial disruption of the ability to conduct normal life functions), a congenital anomaly/birth defect, or may have jeopardized the participant and may have required medical or surgical intervention to prevent intensive treatment in an emergency room or at home (e.g. for allergic bronchospasm, blood dyscrasias or convulsions) that do not result in inpatient hospitalization, development of drug dependency or drug abuse.
Measured in the safety population, which included all participants who received ≥ 1 dose of any study treatment (sitravatinib, nivolumab, pembrolizumab, or enfortumab vedotin).
Posted
Count of Participants
Participants
Day 1 up to approximately 3 years
ID
Title
Description
OG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
Secondary
Number of Participants Who Experienced a Treatment-related Adverse Event
A treatment-related adverse event was defined as an adverse event determined to have a possible causal relationship to the study treatment(s) by the investigator. An adverse event was defined as any reaction, side effect or other undesirable medical event that occurred during participation in a clinical trial. Any clinically significant changes from baseline in laboratory results were recorded as adverse events.
Measured in the safety population, which included all participants who received ≥ 1 dose of any study treatment (sitravatinib, nivolumab, pembrolizumab, or enfortumab vedotin).
Posted
Count of Participants
Participants
Day 1 up to approximately 3 years
ID
Title
Description
OG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
OG001
Cohort 2
Secondary
Duration of Response (DOR)
DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of objective progression of disease (PD) per RECIST V1.1, or to death due to any cause in the absence of documented PD. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare efficacy endpoints across Cohort 9 dose levels.
Measured in the Clinical Activity Evaluable Population-confirmed Response Subset, which included participants who achieved an objective response, received ≥1 dose of study treatment drug, had an evaluable baseline tumor assessment and ≥1 post-baseline tumor assessment. One participant in Cohort 6 who experienced a response wasn't included in DOR analysis because they didn't receive ≥1 dose of study treatment, have an evaluable baseline tumor assessment or ≥1 post-baseline tumor assessment.
Posted
Median
95% Confidence Interval
months
Up to approximately 3 years
ID
Title
Description
OG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
Secondary
Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR) was defined as the number of participants documented to have a confirmed CR, PR, or stable disease (SD), per RECIST V1.1, documented during at least 1 on-study assessment. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis < 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. SD was defined as target lesions increasing by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds.
Measured in the Full Analysis Set, which included participants who received ≥ 1 dose of each study treatment drug (ie, ≥ 1 dose of both sitravatinib and nivolumab for Cohorts 1 to 8, or ≥ 1 dose each of sitravatinib, pembrolizumab, and enfortumab vedotin for Cohort 9). Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare efficacy endpoints across Cohort 9 dose levels.
Posted
Count of Participants
Participants
Up to approximately 3 years
ID
Title
Description
OG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
Secondary
Progression-Free Survival (PFS)
PFS was defined as the time from date of first study treatment to first PD per RECIST V1.1, or death due to any cause in the absence of documented PD.
Measured in the Full Analysis Set, which included participants who received ≥ 1 dose of each study treatment drug (ie, ≥ 1 dose of both sitravatinib and nivolumab for Cohorts 1 to 8, or ≥ 1 dose each of sitravatinib, pembrolizumab, and enfortumab vedotin for Cohort 9). Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare efficacy endpoints across Cohort 9 dose levels.
Posted
Median
95% Confidence Interval
months
Up to approximately 3 years
ID
Title
Description
OG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
OG001
Cohort 2
Secondary
1-Year Survival Rate
Survival was defined as the time from date of first study treatment to death due to any cause. Kaplan-Meier (product limit) estimates of the percentage of participants who died at 1-year was calculated to estimate the 1-year survival rate, defined as the percentage of participants alive at 1 year. Confidence Intervals were calculated based on Greenwood's formula. Participants who discontinued prior to 1-year were censored on the last date that they were known to be alive. For participants with no follow-up after first dose of study drug, survival rate was censored at the date of first dose (Day 1).
Measured in the Full Analysis Set, which included participants who received ≥ 1 dose of each study treatment drug (ie, ≥ 1 dose of both sitravatinib and nivolumab for Cohorts 1 to 8, or ≥ 1 dose each of sitravatinib, pembrolizumab, and enfortumab vedotin for Cohort 9). Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare efficacy endpoints across Cohort 9 dose levels.
Posted
Number
95% Confidence Interval
percentage of participants
1 year
ID
Title
Description
OG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
Secondary
Overall Survival (OS)
OS was defined as the time from date of first study treatment to death due to any cause.
Measured in the Full Analysis Set, which included participants who received ≥ 1 dose of each study treatment drug (ie, ≥ 1 dose of both sitravatinib and nivolumab for Cohorts 1 to 8, or ≥ 1 dose each of sitravatinib, pembrolizumab, and enfortumab vedotin for Cohort 9). Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare efficacy endpoints across Cohort 9 dose levels.
Posted
Median
95% Confidence Interval
months
Up to approximately 3 years
ID
Title
Description
OG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
OG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
Secondary
Geometric Mean Blood Plasma Concentration of Sitravatinib
Blood draws for analysis of blood plasma concentrations of sitravatinib were collected following electrocardiograms and assessment of vital signs. Concentration data below the limit of quantification were set to 0.
Measured in the Pharmacokinetic (PK) Evaluable Population, which included all participants who received treatment with sitravatinib and had available data at each timepoint. Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare PK endpoints across Cohort 9 dose levels.
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
Secondary
Cohort 9 Lead-in Dose Escalation Part Only: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
A DLT was defined as any of the following events considered to be causally related to treatment with sitravatinib in combination with pembrolizumab and enfortumab in the lead-in dose escalation part of Cohort 9 (as pre-specified): hematological DLTs (Grade 4 neutropenia, thrombocytopenia, anemia unexplained by underlying disease, ≥Grade 3 febrile neutropenia or neutropenia with significant clinical sequelae, or any requirement for a platelet transfusion), non-hematological DLTs (≥Grade 4 infusion related reaction, non-hematological toxicity, Grade 3 infusion related reaction that does not resolve within 24 hours, hypertension that cannot be controlled with medical therapy), other Grade 3 non-hematologic toxicity lasting for >3 days, with exceptions, Grade 2 pneumonitis or colitis, ≥Grade 3 non-hematological laboratory abnormalities, alanine transaminase>3 x upper limit of normal (ULN) with bilirubin> 2xULN, and other related toxic effects may have been assessed as DLTs.
Measured in the DLT evaluable population, which, as pre-specified in the statistical analysis plan, was defined as participants who enrolled in the lead-in dose escalation portion of Cohort 9, who experienced a DLT or who cleared the DLT period.
Posted
Count of Participants
Participants
Cycle 1 Day 1 through pre-dose Cycle 2 Day 1 (cycle for Cohort 9 was 21 days)
ID
Title
Description
OG000
Cohort 9 Dose Level 1
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 1 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.25 mg/kg IV infusion on Days 1 and 8 every 3 weeks (Q3W), and pembrolizumab 200 mg Q3W as an IV infusion.
Time Frame
Day 1 up to approximately 3 years
Description
All cause mortality, serious adverse events and other adverse events are reported for all enrolled participants.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cohort 1
Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).
37
49
35
49
49
49
EG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
15
23
15
23
23
23
EG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
15
18
10
18
18
18
EG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
7
9
4
9
9
9
EG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
35
53
26
53
53
53
EG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
12
27
14
27
27
27
EG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
36
56
23
56
56
56
EG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
8
9
3
9
9
9
EG008
Cohort 9 Dose Level 1
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 1 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.25 mg/kg IV infusion on Days 1 and 8 every 3 weeks (Q3W), and pembrolizumab 200 mg Q3W as an IV infusion.
5
8
5
8
8
8
EG009
Cohort 9 Dose Level 2
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 2 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
3
4
1
4
4
4
EG010
Cohort 9 Dose Level 3
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 3 were enrolled to receive sitravatinib 70 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
0
4
3
4
4
4
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG0030 events0 affected9 at risk
EG0041 events1 affected53 at risk
EG0050 events0 affected27 at risk
EG0061 events1 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
Leukocytosis
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Adrenal insufficiency
Endocrine disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hyperthyroidism
Endocrine disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Large intestinal obstruction
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0023 events2 affected18 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0004 events3 affected49 at risk
EG0011 events1 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Asthenia
General disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Chills
General disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Fatigue
General disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Influenza like illness
General disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Infusion site extravasation
General disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0011 events1 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Pyrexia
General disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Corona virus infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Kidney infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Sepsis
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0003 events2 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Skin infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Amylase increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Ejection fraction decreased
Investigations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Lipase increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Tumour pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Headache
Nervous system disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Syncope
Nervous system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0012 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Urinary tract obstruction
Renal and urinary disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0022 events1 affected18 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Embolism
Vascular disorders
MedDRA 21.0
Systematic Assessment
EG0003 events2 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hypertension
Vascular disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Orthostatic hypotension
Vascular disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG00027 events13 affected49 at risk
EG00114 events10 affected23 at risk
EG0024 events2 affected18 at risk
EG0033 events2 affected9 at risk
EG00421 events10 affected53 at risk
EG00527 events10 affected27 at risk
EG00618 events10 affected56 at risk
EG0072 events1 affected9 at risk
EG0083 events2 affected8 at risk
EG0092 events1 affected4 at risk
EG0101 events1 affected4 at risk
Iron deficiency anaemia
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Leukocytosis
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Polycythaemia
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0005 events2 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Thrombocytosis
Blood and lymphatic system disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Cardiomegaly
Cardiac disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0022 events1 affected18 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Supraventricular extrasystoles
Cardiac disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Deafness unilateral
Ear and labyrinth disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Ear haemorrhage
Ear and labyrinth disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Adrenal insufficiency
Endocrine disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0011 events1 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Androgen deficiency
Endocrine disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hyperthyroidism
Endocrine disorders
MedDRA 21.0
Systematic Assessment
EG0005 events4 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Hypogonadism male
Endocrine disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 21.0
Systematic Assessment
EG00020 events19 affected49 at risk
EG0019 events9 affected23 at risk
EG0029 events8 affected18 at risk
EG003
Dry eye
Eye disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Eye disorder
Eye disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Eye pain
Eye disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Eyelid margin crusting
Eye disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Scleral discolouration
Eye disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Vision blurred
Eye disorders
MedDRA 21.0
Systematic Assessment
EG0004 events3 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Vitreous floaters
Eye disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0022 events1 affected18 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0010 events0 affected23 at risk
EG0023 events2 affected18 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0008 events8 affected49 at risk
EG0016 events4 affected23 at risk
EG00210 events8 affected18 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0012 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0011 events1 affected23 at risk
EG0022 events1 affected18 at risk
EG003
Anal haemorrhage
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0022 events1 affected18 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG00020 events16 affected49 at risk
EG00110 events9 affected23 at risk
EG0027 events5 affected18 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG00066 events29 affected49 at risk
EG00152 events20 affected23 at risk
EG00224 events13 affected18 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0017 events6 affected23 at risk
EG0023 events3 affected18 at risk
EG003
Duodenal ulcer
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0011 events1 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0004 events4 affected49 at risk
EG0014 events3 affected23 at risk
EG0024 events3 affected18 at risk
EG003
Faeces discoloured
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0014 events3 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0011 events1 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Gingival pain
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Haemorrhoidal haemorrhage
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Large intestinal obstruction
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG00037 events20 affected49 at risk
EG00118 events12 affected23 at risk
EG0029 events7 affected18 at risk
EG003
Odynophagia
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0005 events2 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Oral dysaesthesia
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0009 events6 affected49 at risk
EG0011 events1 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0003 events2 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Retching
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Small intestinal obstruction
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG00019 events11 affected49 at risk
EG0017 events4 affected23 at risk
EG0029 events7 affected18 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 21.0
Systematic Assessment
EG00023 events15 affected49 at risk
EG0019 events7 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Asthenia
General disorders
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Axillary pain
General disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0022 events1 affected18 at risk
EG003
Chest discomfort
General disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Chills
General disorders
MedDRA 21.0
Systematic Assessment
EG0005 events5 affected49 at risk
EG0011 events1 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Face oedema
General disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Fatigue
General disorders
MedDRA 21.0
Systematic Assessment
EG00067 events35 affected49 at risk
EG00146 events19 affected23 at risk
EG00228 events15 affected18 at risk
EG003
Feeling cold
General disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Gait disturbance
General disorders
MedDRA 21.0
Systematic Assessment
EG0005 events1 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Influenza like illness
General disorders
MedDRA 21.0
Systematic Assessment
EG0002 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Infusion site extravasation
General disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Localised oedema
General disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Malaise
General disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0013 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Mucosal inflammation
General disorders
MedDRA 21.0
Systematic Assessment
EG0004 events4 affected49 at risk
EG0011 events1 affected23 at risk
EG0025 events3 affected18 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0014 events2 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Oedema peripheral
General disorders
MedDRA 21.0
Systematic Assessment
EG00014 events13 affected49 at risk
EG00115 events9 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Pyrexia
General disorders
MedDRA 21.0
Systematic Assessment
EG0009 events6 affected49 at risk
EG0017 events6 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Temperature intolerance
General disorders
MedDRA 21.0
Systematic Assessment
EG0005 events3 affected49 at risk
EG0011 events1 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Candida infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Corona virus infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0002 events1 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Cystitis
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Ear infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Fungal skin infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0012 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hand-foot-and-mouth disease
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Kidney infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Onychomycosis
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0014 events3 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Rash pustular
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Sepsis
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0013 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Skin infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Tooth infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 21.0
Systematic Assessment
EG00016 events8 affected49 at risk
EG00113 events8 affected23 at risk
EG0025 events4 affected18 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0006 events6 affected49 at risk
EG0015 events4 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Medication error
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Muscle strain
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Stoma site haemorrhage
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Subarachnoid haemorrhage
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Subdural haematoma
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Upper limb fracture
Injury, poisoning and procedural complications
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 21.0
Systematic Assessment
EG00022 events17 affected49 at risk
EG00114 events8 affected23 at risk
EG0023 events3 affected18 at risk
EG003
Amylase increased
Investigations
MedDRA 21.0
Systematic Assessment
EG00015 events10 affected49 at risk
EG0015 events5 affected23 at risk
EG0023 events3 affected18 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 21.0
Systematic Assessment
EG00019 events14 affected49 at risk
EG00111 events9 affected23 at risk
EG0025 events5 affected18 at risk
EG003
Blood albumin decreased
Investigations
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0009 events8 affected49 at risk
EG00113 events5 affected23 at risk
EG0023 events3 affected18 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0003 events2 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 21.0
Systematic Assessment
EG00021 events10 affected49 at risk
EG00110 events9 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Blood glucose increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0004 events3 affected49 at risk
EG0012 events2 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Blood thyroid stimulating hormone decreased
Investigations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Blood thyroid stimulating hormone increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0016 events6 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Blood triglycerides increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Blood urea increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0005 events2 affected49 at risk
EG0011 events1 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Ejection fraction decreased
Investigations
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0012 events2 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Lipase increased
Investigations
MedDRA 21.0
Systematic Assessment
EG00022 events10 affected49 at risk
EG0017 events6 affected23 at risk
EG0029 events5 affected18 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA 21.0
Systematic Assessment
EG0006 events5 affected49 at risk
EG0017 events4 affected23 at risk
EG0025 events3 affected18 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Platelet count decreased
Investigations
MedDRA 21.0
Systematic Assessment
EG0007 events5 affected49 at risk
EG0015 events3 affected23 at risk
EG00210 events4 affected18 at risk
EG003
Troponin T increased
Investigations
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Weight decreased
Investigations
MedDRA 21.0
Systematic Assessment
EG00025 events15 affected49 at risk
EG00120 events13 affected23 at risk
EG00210 events4 affected18 at risk
EG003
White blood cell count decreased
Investigations
MedDRA 21.0
Systematic Assessment
EG0004 events2 affected49 at risk
EG0010 events0 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Cachexia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG00041 events23 affected49 at risk
EG00126 events18 affected23 at risk
EG00221 events12 affected18 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0006 events5 affected49 at risk
EG0013 events3 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Glucose tolerance impaired
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0013 events3 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0009 events6 affected49 at risk
EG0017 events3 affected23 at risk
EG0027 events2 affected18 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG00011 events3 affected49 at risk
EG0014 events3 affected23 at risk
EG0022 events1 affected18 at risk
EG003
Hyperlipidaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hypertriglyceridaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0006 events4 affected49 at risk
EG0015 events3 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG00014 events9 affected49 at risk
EG00110 events7 affected23 at risk
EG0026 events3 affected18 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0007 events3 affected49 at risk
EG0012 events2 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0012 events2 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0008 events6 affected49 at risk
EG0017 events4 affected23 at risk
EG0024 events1 affected18 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG00012 events6 affected49 at risk
EG0016 events4 affected23 at risk
EG00210 events5 affected18 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Iron deficiency
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Vitamin B12 deficiency
Metabolism and nutrition disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG00016 events11 affected49 at risk
EG0014 events3 affected23 at risk
EG0022 events1 affected18 at risk
EG003
Arthritis
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0012 events2 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0006 events6 affected49 at risk
EG0017 events6 affected23 at risk
EG0027 events4 affected18 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Coccydynia
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0004 events4 affected49 at risk
EG0014 events4 affected23 at risk
EG0022 events2 affected18 at risk
EG003
Gouty arthritis
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0002 events1 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0014 events4 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG00112 events7 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0011 events1 affected23 at risk
EG0020 events0 affected18 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0013 events3 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0000 events0 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0003 events3 affected49 at risk
EG0010 events0 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0001 events1 affected49 at risk
EG0012 events2 affected23 at risk
EG0021 events1 affected18 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 21.0
Systematic Assessment
EG0002 events2 affected49 at risk
EG0017 events2 affected23 at risk
EG0023 events3 affected18 at risk
EG003
Tumour pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG008
Cohort 9 Dose Level 1
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 1 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.25 mg/kg IV infusion on Days 1 and 8 every 3 weeks (Q3W), and pembrolizumab 200 mg Q3W as an IV infusion.
OG009
Cohort 9 Dose Level 2
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 2 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
OG010
Cohort 9 Dose Level 3
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 3 were enrolled to receive sitravatinib 70 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
Units
Counts
Participants
OG00049
OG00123
OG00218
OG0039
OG00453
OG00527
OG00656
OG0079
OG0088
OG0094
OG0104
Title
Denominators
Categories
Title
Measurements
OG00049
OG00123
OG00218
OG0039
OG00453
OG00527
OG00656
OG0079
OG0088
OG0094
OG0104
OG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG008
Cohort 9 Dose Level 1
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 1 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.25 mg/kg IV infusion on Days 1 and 8 every 3 weeks (Q3W), and pembrolizumab 200 mg Q3W as an IV infusion.
OG009
Cohort 9 Dose Level 2
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 2 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
OG010
Cohort 9 Dose Level 3
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 3 were enrolled to receive sitravatinib 70 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
Units
Counts
Participants
OG00049
OG00123
OG00218
OG0039
OG00453
OG00527
OG00656
OG0079
OG0088
OG0094
OG0104
Title
Denominators
Categories
Title
Measurements
OG00035
OG00115
OG00210
OG0034
OG00426
OG00514
OG00623
OG0073
OG0085
OG0091
OG0103
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG008
Cohort 9 Dose Level 1
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 1 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.25 mg/kg IV infusion on Days 1 and 8 every 3 weeks (Q3W), and pembrolizumab 200 mg Q3W as an IV infusion.
OG009
Cohort 9 Dose Level 2
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 2 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
OG010
Cohort 9 Dose Level 3
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 3 were enrolled to receive sitravatinib 70 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
Units
Counts
Participants
OG00049
OG00123
OG00218
OG0039
OG00453
OG00527
OG00656
OG0079
OG0088
OG0094
OG0104
Title
Denominators
Categories
Title
Measurements
Sitravatinib Related
OG00043
OG00123
OG00218
OG0038
OG00451
OG00526
OG00652
OG0079
OG0088
OG0094
OG0103
Nivolumab Related
OG00041
OG00123
OG00215
OG0037
OG004
Pembrolizumab Related
OG000NAAs pre-specified, participants did not receive pembrolizumab treatment in this Cohort.
OG001NAAs pre-specified, participants did not receive pembrolizumab treatment in this Cohort.
OG002NAAs pre-specified, participants did not receive pembrolizumab treatment in this Cohort.
OG003
Enfortumab Vedotin Related
OG000NAAs pre-specified, participants did not receive enfortumab vedotin treatment in this Cohort.
OG001NAAs pre-specified, participants did not receive enfortumab vedotin treatment in this Cohort.
OG002NAAs pre-specified, participants did not receive enfortumab vedotin treatment in this Cohort.
OG003
OG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG008
Cohort 9
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants were enrolled to 3 dose levels of sitravatinib in combination with pembrolizumab and enfortumab vedotin. Sitravatinib was received orally via capsules QD in 21-day cycles at doses 35 mg and 70 mg. Pembrolizumab was received as an IV infusion over approximately 30 minutes (± 5 minutes) at 200 mg every 3 weeks (Q3W), in accordance with the current pembrolizumab USPI. Enfortumab vedotin dosing was based on participant weight, starting at 1.25 mg/kg up to 125 mg/kg QD, with a dose de-escalation step to 1 mg/kg. Enfortumab vedotin was received as an IV infusion over approximately 30 minutes (± 5 minutes) on Days 1 and 8 of a 21-day cycle.
Units
Counts
Participants
OG0006
OG0015
OG0024
OG0030
OG00417
OG0058
OG0063
OG0070
OG0084
Title
Denominators
Categories
Title
Measurements
OG0005.585(3.844 to NA)Upper confidence intervals could not be calculated due to the low number of participants with a response.
OG0019.478(5.782 to NA)Upper confidence intervals could not be calculated due to the low number of participants with a response.
OG00211.762(7.392 to NA)Upper confidence intervals could not be calculated due to the low number of participants with a response.
OG0047.326(5.520 to 12.977)
OG00516.361(5.552 to NA)Upper confidence intervals could not be calculated due to the low number of participants with a response.
OG0067.425(5.552 to NA)Upper confidence intervals could not be calculated due to the low number of participants with a response.
OG00811.8(4.70 to NA)Upper confidence intervals could not be calculated due to the low number of participants with a response.
OG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG008
Cohort 9
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants were enrolled to 3 dose levels of sitravatinib in combination with pembrolizumab and enfortumab vedotin. Sitravatinib was received orally via capsules QD in 21-day cycles at doses 35 mg and 70 mg. Pembrolizumab was received as an IV infusion over approximately 30 minutes (± 5 minutes) at 200 mg every 3 weeks (Q3W), in accordance with the current pembrolizumab USPI. Enfortumab vedotin dosing was based on participant weight, starting at 1.25 mg/kg up to 125 mg/kg QD, with a dose de-escalation step to 1 mg/kg. Enfortumab vedotin was received as an IV infusion over approximately 30 minutes (± 5 minutes) on Days 1 and 8 of a 21-day cycle.
Units
Counts
Participants
OG00049
OG00123
OG00218
OG0039
OG00453
OG00527
OG00656
OG0079
OG00816
Title
Denominators
Categories
Title
Measurements
OG00032
OG00119
OG00212
OG0037
OG00435
OG00517
OG00633
OG0076
OG00810
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG008
Cohort 9
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants were enrolled to 3 dose levels of sitravatinib in combination with pembrolizumab and enfortumab vedotin. Sitravatinib was received orally via capsules QD in 21-day cycles at doses 35 mg and 70 mg. Pembrolizumab was received as an IV infusion over approximately 30 minutes (± 5 minutes) at 200 mg every 3 weeks (Q3W), in accordance with the current pembrolizumab USPI. Enfortumab vedotin dosing was based on participant weight, starting at 1.25 mg/kg up to 125 mg/kg QD, with a dose de-escalation step to 1 mg/kg. Enfortumab vedotin was received as an IV infusion over approximately 30 minutes (± 5 minutes) on Days 1 and 8 of a 21-day cycle.
Units
Counts
Participants
OG00049
OG00123
OG00218
OG0039
OG00453
OG00527
OG00656
OG0079
OG00816
Title
Denominators
Categories
Title
Measurements
OG0003.877(2.497 to 5.487)
OG0017.786(3.943 to 14.620)
OG0023.910(1.873 to 9.133)
OG0033.515(1.971 to NA)Upper confidence intervals could not be calculated due to the low number of participants with a documented PD or death.
OG0043.943(3.450 to 5.651)
OG0055.421(3.220 to 18.168)
OG0063.680(2.234 to 5.520)
OG0073.713(1.840 to NA)Upper confidence intervals could not be calculated due to the low number of participants with a documented PD or death.
OG0084.0(2.04 to 6.51)
OG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG008
Cohort 9
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants were enrolled to 3 dose levels of sitravatinib in combination with pembrolizumab and enfortumab vedotin. Sitravatinib was received orally via capsules QD in 21-day cycles at doses 35 mg and 70 mg. Pembrolizumab was received as an IV infusion over approximately 30 minutes (± 5 minutes) at 200 mg every 3 weeks (Q3W), in accordance with the current pembrolizumab USPI. Enfortumab vedotin dosing was based on participant weight, starting at 1.25 mg/kg up to 125 mg/kg QD, with a dose de-escalation step to 1 mg/kg. Enfortumab vedotin was received as an IV infusion over approximately 30 minutes (± 5 minutes) on Days 1 and 8 of a 21-day cycle.
Units
Counts
Participants
OG00049
OG00123
OG00218
OG0039
OG00453
OG00527
OG00656
OG0079
OG00816
Title
Denominators
Categories
Title
Measurements
OG00042.5(27.9 to 56.4)
OG00156.5(34.3 to 73.8)
OG00255.6(30.5 to 74.8)
OG00344.4(13.6 to 71.9)
OG00453.9(39.5 to 66.3)
OG00557.1(36.0 to 73.6)
OG00632.6(19.5 to 46.3)
OG00716.7(1.1 to 49.3)
OG00841.5(15.4 to 66.1)
OG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG008
Cohort 9
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants were enrolled to 3 dose levels of sitravatinib in combination with pembrolizumab and enfortumab vedotin. Sitravatinib was received orally via capsules QD in 21-day cycles at doses 35 mg and 70 mg. Pembrolizumab was received as an IV infusion over approximately 30 minutes (± 5 minutes) at 200 mg every 3 weeks (Q3W), in accordance with the current pembrolizumab USPI. Enfortumab vedotin dosing was based on participant weight, starting at 1.25 mg/kg up to 125 mg/kg QD, with a dose de-escalation step to 1 mg/kg. Enfortumab vedotin was received as an IV infusion over approximately 30 minutes (± 5 minutes) on Days 1 and 8 of a 21-day cycle.
Units
Counts
Participants
OG00049
OG00123
OG00218
OG0039
OG00453
OG00527
OG00656
OG0079
OG00816
Title
Denominators
Categories
Title
Measurements
OG0008.049(4.632 to 15.967)
OG00115.639(7.655 to NA)Data could not be calculated as too few participants experienced an event.
OG00212.945(5.618 to 22.439)
OG0035.092(1.971 to 24.279)
OG00413.405(5.782 to 21.290)
OG005NA(5.947 to NA)Data could not be calculated as too few participants experienced an event.
OG0068.969(7.359 to 10.809)
OG0077.556(2.825 to 9.922)
OG00810.8(2.69 to NA)Data could not be calculated as too few participants experienced an event.
OG001
Cohort 2
Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG002
Cohort 3
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG003
Cohort 4
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG004
Cohort 5
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG005
Cohort 6
Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG006
Cohort 7
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG007
Cohort 8
Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8.
Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.
OG008
Cohort 9
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants were enrolled to 3 dose levels of sitravatinib in combination with pembrolizumab and enfortumab vedotin. Sitravatinib was received orally via capsules QD in 21-day cycles at doses 35 mg and 70 mg. Pembrolizumab was received as an IV infusion over approximately 30 minutes (± 5 minutes) at 200 mg every 3 weeks (Q3W), in accordance with the current pembrolizumab USPI. Enfortumab vedotin dosing was based on participant weight, starting at 1.25 mg/kg up to 125 mg/kg QD, with a dose de-escalation step to 1 mg/kg. Enfortumab vedotin was received as an IV infusion over approximately 30 minutes (± 5 minutes) on Days 1 and 8 of a 21-day cycle.
Units
Counts
Participants
OG00049
OG00123
OG00217
OG0039
OG00453
OG00527
OG00656
OG0079
OG00816
Title
Denominators
Categories
Cycle 1 Day 1 Pre-dose
ParticipantsOG00046
ParticipantsOG00121
ParticipantsOG00216
ParticipantsOG0039
ParticipantsOG00450
ParticipantsOG00524
ParticipantsOG00646
ParticipantsOG0078
ParticipantsOG00816
Title
Measurements
OG0000± 0
OG0010± 0
OG0020± 0
OG003
Cycle 1 Day 1 30 Min Post-Dose
ParticipantsOG00034
ParticipantsOG00115
ParticipantsOG00215
ParticipantsOG0036
Cycle 1 Day 1 2 Hours Post-Dose
ParticipantsOG0007
ParticipantsOG0010
ParticipantsOG0021
ParticipantsOG0030
Cycle 1 Day 1 4 Hours Post-Dose
ParticipantsOG00044
ParticipantsOG00112
ParticipantsOG00210
ParticipantsOG0035
Cycle 1 Day 1 6 Hours Post-Dose
ParticipantsOG0007
ParticipantsOG0010
ParticipantsOG0021
ParticipantsOG0030
Cycle 1 Day 1 7 Hours Post-Dose
ParticipantsOG0001
ParticipantsOG0016
ParticipantsOG0022
ParticipantsOG0034
Cycle 1 Day 1 8 Hours Post-Dose
ParticipantsOG0006
ParticipantsOG0010
ParticipantsOG0021
ParticipantsOG0030
Cycle 1 Day 1 24 Hours Post-Dose
ParticipantsOG0006
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Cycle 1 Day 15 Pre-Dose
ParticipantsOG00037
ParticipantsOG00115
ParticipantsOG00212
ParticipantsOG0038
Cycle 1 Day 15 30 Min Post-Dose
ParticipantsOG0006
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Cycle 1 Day 15 2 Hours Post-Dose
ParticipantsOG0008
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Cycle 1 Day 15 4 Hours Post-Dose
ParticipantsOG00034
ParticipantsOG0017
ParticipantsOG00210
ParticipantsOG0034
Cycle 1 Day 15 6 Hours Post-Dose
ParticipantsOG0007
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Cycle 1 Day 15 7 Hours Post-Dose
ParticipantsOG0000
ParticipantsOG0013
ParticipantsOG0022
ParticipantsOG0034
Cycle 1 Day 15 8 Hours Post-Dose
ParticipantsOG0007
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Cycle 1 Day 15 24 Hours Post-Dose
ParticipantsOG0006
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Cycle 2 Day 1 Pre-Dose
ParticipantsOG00031
ParticipantsOG00117
ParticipantsOG00216
ParticipantsOG0037
Cycle 2 Day 1 7 Hours Post-Dose
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Cycle 2 Day 8 Pre-Dose
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Cycle 3 Day 1 Pre-Dose
ParticipantsOG00023
ParticipantsOG00115
ParticipantsOG0028
ParticipantsOG0034
Cycle 3 Day 8 Pre-Dose
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Cycle 5 Day 1 Pre-Dose
ParticipantsOG00016
ParticipantsOG0019
ParticipantsOG0028
ParticipantsOG0033
Cycle 6 Day 8 Pre-Dose
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
OG001
Cohort 9 Dose Level 2
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 2 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
OG002
Cohort 9 Dose Level 3
Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled.
During the lead-in dose-escalation part, participants in Cohort 9 Dose Level 3 were enrolled to receive sitravatinib 70 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
Units
Counts
Participants
OG0008
OG0014
OG0024
Title
Denominators
Categories
Title
Measurements
OG0002
OG0010
OG0022
0 events
0 affected
9 at risk
EG0041 events1 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0041 events1 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0042 events2 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0071 events1 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0052 events2 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
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EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0041 events1 affected53 at risk
EG0051 events1 affected27 at risk
EG0062 events2 affected56 at risk
EG0070 events0 affected9 at risk
EG0082 events2 affected8 at risk
EG0090 events0 affected4 at risk
EG0101 events1 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0051 events1 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0043 events3 affected53 at risk
EG0053 events1 affected27 at risk
EG0061 events1 affected56 at risk
EG0070 events0 affected9 at risk
EG0083 events2 affected8 at risk
EG0092 events1 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0048 events7 affected53 at risk
EG0053 events3 affected27 at risk
EG0062 events2 affected56 at risk
EG0071 events1 affected9 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0051 events1 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
4 events
3 affected
9 at risk
EG00417 events13 affected53 at risk
EG0056 events5 affected27 at risk
EG00612 events5 affected56 at risk
EG0076 events2 affected9 at risk
EG0080 events0 affected8 at risk
EG0094 events2 affected4 at risk
EG0101 events1 affected4 at risk
1 events
1 affected
9 at risk
EG0047 events7 affected53 at risk
EG0053 events3 affected27 at risk
EG0066 events6 affected56 at risk
EG0070 events0 affected9 at risk
EG0083 events2 affected8 at risk
EG0094 events1 affected4 at risk
EG0102 events2 affected4 at risk
0 events
0 affected
9 at risk
EG0043 events3 affected53 at risk
EG0052 events1 affected27 at risk
EG0063 events3 affected56 at risk
EG0070 events0 affected9 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0102 events1 affected4 at risk
0 events
0 affected
9 at risk
EG00415 events11 affected53 at risk
EG0057 events6 affected27 at risk
EG0065 events5 affected56 at risk
EG0071 events1 affected9 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected4 at risk
EG0103 events3 affected4 at risk
2 events
1 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0041 events1 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0102 events1 affected4 at risk
1 events
1 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0046 events5 affected53 at risk
EG0050 events0 affected27 at risk
EG0063 events2 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
1 events
1 affected
9 at risk
EG0042 events2 affected53 at risk
EG0052 events2 affected27 at risk
EG0062 events2 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
0 events
0 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
5 events
4 affected
9 at risk
EG00429 events21 affected53 at risk
EG00515 events12 affected27 at risk
EG00643 events27 affected56 at risk
EG0074 events4 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0103 events3 affected4 at risk
0 events
0 affected
9 at risk
EG0042 events2 affected53 at risk
EG0053 events3 affected27 at risk
EG0061 events1 affected56 at risk
EG0072 events1 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected4 at risk
1 events
1 affected
9 at risk
EG0040 events0 affected53 at risk
EG0050 events0 affected27 at risk
EG0060 events0 affected56 at risk
EG0070 events0 affected9 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected4 at risk
EG0101 events1 affected4 at risk
41
OG00524
OG00635
OG0074
OG008NAAs pre-specified, participants did not receive nivolumab treatment in this Cohort.
OG009NAAs pre-specified, participants did not receive nivolumab treatment in this Cohort.
OG010NAAs pre-specified, participants did not receive nivolumab treatment in this Cohort.
NA
As pre-specified, participants did not receive pembrolizumab treatment in this Cohort.
OG004NAAs pre-specified, participants did not receive pembrolizumab treatment in this Cohort.
OG005NAAs pre-specified, participants did not receive pembrolizumab treatment in this Cohort.
OG006NAAs pre-specified, participants did not receive pembrolizumab treatment in this Cohort.
OG007NAAs pre-specified, participants did not receive pembrolizumab treatment in this Cohort.
OG0086
OG0093
OG0103
NA
As pre-specified, participants did not receive enfortumab vedotin treatment in this Cohort.
OG004NAAs pre-specified, participants did not receive enfortumab vedotin treatment in this Cohort.
OG005NAAs pre-specified, participants did not receive enfortumab vedotin treatment in this Cohort.
OG006NAAs pre-specified, participants did not receive enfortumab vedotin treatment in this Cohort.
OG007NAAs pre-specified, participants did not receive enfortumab vedotin treatment in this Cohort.
OG0087
OG0094
OG0104
0
± 0
OG0040± 0
OG0050± 0
OG0060± 0
OG0070± 0
OG0080± 0
ParticipantsOG00441
ParticipantsOG00518
ParticipantsOG00642
ParticipantsOG0077
ParticipantsOG00812
Title
Measurements
OG0001.85± 300.88
OG0010.82± 10.95
OG0021.56± 176.68
OG0030.91± 499.94
OG0041.25± 266.58
OG0051.28± 231.33
OG0061.40± 268.79
OG0070.25± 248.74
OG0080.40± 172.86
ParticipantsOG0041
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0070
ParticipantsOG0080
Title
Measurements
OG0005.69± 117.10
OG0026.94± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
OG00424.90± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
ParticipantsOG00426
ParticipantsOG0050
ParticipantsOG0061
ParticipantsOG0070
ParticipantsOG0080
Title
Measurements
OG00016.55± 168.43
OG00121.46± 122.57
OG00231.21± 80.61
OG00318.33± 158.02
OG00423.72± 104.51
OG00635.20± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
ParticipantsOG0041
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0070
ParticipantsOG0080
Title
Measurements
OG00023.16± 69.50
OG00211.70± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
OG00415.50± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
ParticipantsOG00413
ParticipantsOG0057
ParticipantsOG00621
ParticipantsOG0075
ParticipantsOG00811
Title
Measurements
OG00027.40± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
OG00122.90± 121.87
OG00220.08± 167.73
OG00315.36± 108.29
OG00423.13± 167.10
OG00523.13± 126.44
OG00637.99± 50.79
OG00731.21± 39.99
OG00810.56± 41.43
ParticipantsOG0041
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0070
ParticipantsOG0080
Title
Measurements
OG00026.08± 72.20
OG00212.10± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
OG00423.00± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
ParticipantsOG0041
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0070
ParticipantsOG0080
Title
Measurements
OG00024.82± 71.41
OG00426.30± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
ParticipantsOG00434
ParticipantsOG0059
ParticipantsOG00634
ParticipantsOG0074
ParticipantsOG0080
Title
Measurements
OG00066.00± 52.30
OG00150.21± 92.49
OG00242.03± 232.08
OG00355.22± 34.39
OG00450.58± 51.48
OG00570.11± 67.12
OG00649.94± 60.28
OG00747.01± 39.78
ParticipantsOG0041
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0070
ParticipantsOG0080
Title
Measurements
OG00054.47± 77.06
OG00475.00± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
ParticipantsOG0041
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0070
ParticipantsOG0080
Title
Measurements
OG00062.50± 44.94
OG00467.80± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
ParticipantsOG00421
ParticipantsOG0053
ParticipantsOG0062
ParticipantsOG0071
ParticipantsOG0080
Title
Measurements
OG00070.90± 49.99
OG00168.77± 23.87
OG00252.36± 111.45
OG00395.35± 3.65
OG00468.67± 52.79
OG00545.27± 21.03
OG00650.71± 33.36
OG00755.30± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
ParticipantsOG0041
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0070
ParticipantsOG0080
Title
Measurements
OG00067.45± 55.03
OG00482.90± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
ParticipantsOG0049
ParticipantsOG0053
ParticipantsOG00619
ParticipantsOG0072
ParticipantsOG0080
Title
Measurements
OG00189.19± 10.73
OG00281.09± 85.63
OG00362.78± 22.36
OG00475.08± 45.43
OG005104.61± 26.97
OG00676.70± 51.05
OG00786.04± 2.22
ParticipantsOG0041
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0070
ParticipantsOG0080
Title
Measurements
OG00072.12± 58.96
OG00495.20± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.
ParticipantsOG0041
ParticipantsOG0050
ParticipantsOG0060
ParticipantsOG0070
ParticipantsOG0080
Title
Measurements
OG00059.88± 52.20
OG00485.20± NAGeometric coefficient of variation could not be calculated as there was only 1 participant with evaluable PK samples at this time point.