A Study of Efficacy and Safety of LAG525 in Combination W... | NCT03499899 | Trialant
NCT03499899
Sponsor
Novartis Pharmaceuticals
Status
Completed
Last Update Posted
Jan 30, 2023Actual
Enrollment
88Actual
Phase
Phase 2
Conditions
Triple-negative Breast Cancer
Interventions
LAG525
PDR001
Carboplatin
Countries
United States
Argentina
Australia
Belgium
Canada
France
Germany
Hungary
Israel
Italy
Japan
Lebanon
Singapore
South Korea
Spain
Taiwan
Thailand
Protocol Section
Identification Module
NCT ID
NCT03499899
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CLAG525B2101
Secondary IDs
ID
Type
Description
Link
2017-004865-28
EudraCT Number
Brief Title
A Study of Efficacy and Safety of LAG525 in Combination With Spartalizumab, or With Spartalizumab and Carboplatin, or With Carboplatin, in Patients With Advanced Triple-negative Breast Cancer
Official Title
A Phase II Open-label, Randomized, Three-arm, Multicenter Study of LAG525 Given in Combination With Spartalizumab (PDR001), or With Spartalizumab and Carboplatin, or With Carboplatin, as First or Second Line Therapy in Patients With Advanced Triple-negative Breast Cancer
Acronym
Not provided
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Jan 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 2, 2018Actual
Primary Completion Date
Feb 27, 2020Actual
Completion Date
Nov 24, 2021Actual
First Submitted Date
Mar 26, 2018
First Submission Date that Met QC Criteria
Apr 9, 2018
First Posted Date
Apr 17, 2018Actual
Results Waived
Not provided
Results First Submitted Date
Apr 20, 2022
Results First Submitted that Met QC Criteria
Apr 20, 2022
Results First Posted Date
May 13, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Apr 22, 2020
Certification/Extension First Submitted that Passed QC Review
Apr 22, 2020
Certification/Extension First Posted Date
Apr 27, 2020Actual
Last Update Submitted Date
Jan 27, 2023
Last Update Posted Date
Jan 30, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
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 main purpose of this study was to assess the antitumor activity of three combinations: i) LAG525 + spartalizumab; ii) LAG525 + spartalizumab + carboplatin, and iii) LAG525 + carboplatin in participants with advanced triple-negative breast cancer (TNBC) in first or second line therapy.
Detailed Description
This was an open-label, Phase II, randomized, multicenter study to assess the efficacy, safety, and pharmacokinetic characteristics of the following three combinations: LAG525 + spartalizumab (PDR001) (Arm 1), LAG525 + spartalizumab (PDR001) + carboplatin (Arm 2), and LAG525 + carboplatin (Arm 3) in participants with advanced triple-negative breast cancer (TNBC) which progressed after adjuvant or one prior line of systemic therapy for metastatic disease.
Participants were assigned to one of the three treatment arms in a ratio of 1:1:1. In protocol amendment 3 (released on 28-Mar-2019), enrollment to treatment Arm 1 (LAG525 + spartalizumab) was prematurely closed due to a higher discontinuation rate due to progressive disease and all subsequent enrolled patients were randomized to Arms 2 and 3 only, in a ratio of 1:1.
Study treatment continued until disease progression, unacceptable toxicity, pregnancy, investigator/participant decision, start of a new anti-neoplastic therapy, withdrawal of consent, lost to follow-up, death, or study was terminated by the sponsor. The investigator might decide to stop carboplatin after 6 cycles, even if the above criteria were not met. Participants who continued to derive clinical benefit from the treatment based on the investigator's evaluation following their completion of this trial might receive post-trial access (PTA) i.e. rollover protocol or a post-study drug supply (PSDS).
The end of study was defined as the earliest occurrence of one of the following: (1) all participants had died or (2) discontinued from the study, or (3) another clinical study became available that could continue to provide study treatment in this participant population and all ongoing participants were eligible to be transferred to that clinical study.
Conditions Module
Conditions
Triple-negative Breast Cancer
Keywords
advanced triple-negative breast cancer
triple-negative breast cancer
checkpoint inhibition
LAG525
spartalizumab
PDR001
carboplatin
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
88Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
LAG525 + PDR001
Experimental
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
Drug: LAG525
Drug: PDR001
LAG525 + PDR001 + carboplatin
Experimental
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
Drug: LAG525
Drug: PDR001
Drug: Carboplatin
LAG525 + carboplatin
Experimental
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Drug: LAG525
Drug: Carboplatin
Interventions
Name
Type
Description
Arm Group Labels
Other Names
LAG525
Drug
LAG525 was a concentrate for solution for intravenous infusion, came in 100mg vials as a liquid formulation for infusion and was dosed at 400mg every 21 days. For all arms, LAG525 was infused first
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Overall Response Rate (ORR) Per Investigator's Assessment According to RECIST v1.1
Overall response rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 based on investigator's assessment. The 95% CIs were computed using two-sided exact binomial method.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Up to approximately 14 months
Secondary Outcomes
Measure
Description
Time Frame
Clinical Benefit Rate (CBR) Per Investigator's Assessment According to RECIST v1.1
CBR is defined as the percentage of participants with a best overall response (BOR) of confirmed CR or PR, or stable disease (SD) lasting 24 weeks or longer, according to RECIST 1.1 criteria. The 95% CI were computed using two-sided exact binomial method.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Had advanced (loco-regionally recurrent not amenable to curative therapy or metastatic) breast cancer
Had adequate bone marrow and organ function.
Had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Had measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (Tumor lesions previously irradiated or subjected to other loco-regional therapy was to be considered measurable if disease progression at the treated site after completion of therapy is clearly documented)
Progressed after adjuvant or 1 prior systemic treatment in the metastatic setting. Patients with de novo metastatic disease were eligible if they received 1 prior line of therapy
Had received prior systemic treatment that included taxane-based chemotherapy for adjuvant or metastatic disease
Had a site of disease amenable to biopsy, and was willing to undergo a new tumor biopsy at screening and during therapy on this study, the latter if medically feasible. Patients with an available archival tumor tissue did not need to perform a tumor biopsy at screening if patient had not received anti-cancer therapy since the biopsy was taken.
Had histologically and/or cytologically confirmed diagnosis of advanced TNBC (based on most recently analyzed biopsy from locally recurrent or metastatic site, local lab) meeting the following criteria: HER2 negative in situ hybridization test or an IHC status of 0 or 1+, and ER and PR expression was <1 percent as determined by immunohistochemistry (IHC)
Exclusion Criteria:
Had received prior immune checkpoint inhibitors as anticancer treatment such as anti-LAG-3, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody (any line of therapy)
Received prior neoadjuvant or adjuvant therapy with a platinum agent or mitomycin and experienced recurrence within 12 months after the end of the platinum-based or mitomycin containing therapy or received Platinum or mitomycin for metastatic disease
Had major surgery within 14 days prior to starting study treatment or had not recovered to grade 1 or less from major side effects
Presence of CTCAE grade 2 toxicity or higher due to prior cancer therapy. Exception to this criterion; patients with any grade of alopecia were allowed to enter the study.
Had received radiotherapy ≤ 4 weeks prior to randomization (≤ 2 weeks for limited field radiation for palliation), and had not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia)
Had a known hypersensitivity to other monoclonal antibodies, platinum-containing compounds, or to any of the excipients of LAG525, spartalizumab, or carboplatin
Had symptomatic central nervous system (CNS) metastases or CNS metastases that required local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within the 2 weeks prior to first dose of study treatment. Patients with treated brain metastases would be neurologically stable and without CNS progression for at least 12 weeks prior to randomization and had discontinued corticosteroid treatment (with the exception of < 10 mg/day of prednisone or equivalent for an indication other than CNS metastases) for at least 4 weeks before first dose of any study treatment
Had clinically significant cardiac disease or impaired cardiac 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
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Ironwood Cancer and Research Centers
Chandler
Arizona
85224
United States
Highlands Oncology Group
References Module
Citations
Not provided
See Also Links
Label
URL
A Plain Language Trial Summary is available on novctrd.com
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
A total of 132 participants were screened of which 88 participants were enrolled in the study and 87 participants received at least one dose of study treatment (1 participant was not treated due to physician decision)
Recruitment Details
The study was conducted across 33 centers in 17 countries.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
FG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
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
Feb 15, 2021
Apr 20, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
United Kingdom
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
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
LAG525 + PDR001
LAG525 + PDR001 + carboplatin
LAG525 + carboplatin
PDR001
Drug
Spartalizumab was a concentrate for solution for intravenous infusion, came in 100mg vials as a liquid formulation for infusion and was dosed at 300mg every 21 days. Spartalizumab was infused after LAG525
LAG525 + PDR001
LAG525 + PDR001 + carboplatin
Spartalizumab
Carboplatin
Drug
Carboplatin was a concentrate for solution for intravenous infusion, came in 100mg/mL and was dosed per area under the curve (AUC) 6 every 21 days. Carboplatin was infused once LAG525 and spartalizumab infusions were completed
LAG525 + PDR001 + carboplatin
LAG525 + carboplatin
Up to approximately 14 months
Duration of Response (DOR) Per Investigator's Assessment According to RECIST v1.1
DOR is the time between the first documented response (CR or PR) and the first documented progression or death due to underlying cancer based on RECIST1.1 and as per investigator's assessment. The DOR distribution was estimated using the Kaplan-Meier method and the 95% confidence intervals using the method of Brookmeyer and Crowley. If progression or death did not occur, the participant was censored at the date of last adequate tumor assessment.
CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Progression: at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. The sum must also demonstrate an absolute increase of at least 5 mm.
From first documented response up to disease progression or death due to underlying cancer, whichever occurs first, up to approximately 14 months
Time to Response (TTR) Per Investigator's Assessment According to RECIST v1.1
TTR is the time from date of randomization to first documented response of CR or PR based on investigators' assessment and according to RECIST 1.1. Median TTR was summarized using descriptive statistics.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
From date of randomization to first documented response (CR or PR), up to approximately 14 months
Progression Free Survival (PFS)
PFS is defined as time from date of randomization to the date of first documented progression or death due to any cause. PFS was assessed via investigator's assessment according to RECIST 1.1. PFS was censored at the date of the last adequate tumor assessment if no PFS event was observed prior to the analysis cut-off date or before the start of the new anticancer therapy date, whichever is earlier. The PFS distribution was estimated using the Kaplan-Meier method. The 95% confidence intervals were calculated using the method of Brookmeyer and Crowley.
From date of randomization to disease progression or death due to any cause, whichever occurs first, up to approximately 14 months
Overall Survival (OS)
OS is defined as the time from date of randomization to date of death due to any cause. If a participant was not known to have died, then OS was censored at the latest date the participant was known to be alive (on or before the cut-off date). The OS distribution was estimated using the Kaplan-Meier method. The 95% confidence intervals were calculated using the method of Brookmeyer and Crowley
From date of randomization to date of death due to any cause, up to 18 months
Pharmacokinetics (PK) Parameter, Area Under the Plasma Concentration Versus Time Curve From Time 0 to 504 Hours (AUC0-504h) of LAG525
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-504h was defined as the area under the plasma concentration-time curve from time zero to 504h.
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
PK Parameter, Cmax of LAG525
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed plasma LAG525 concentration
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
PK Parameter, AUClast of LAG525
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of LAG525
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
PK Parameter, Tmax of LAG525
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum LAG525 serum concentration. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
PK Parameter, AUC0-504h of PDR001
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-504h was defined as the area under the plasma concentration-time curve from time zero to 504h.
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
PK Parameter, Cmax of PDR001
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed PDR001 serum concentration
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
PK Parameter, AUClast of PDR001
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of PDR001
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
PK Parameter, Tmax of PDR001
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum PDR001 serum concentration. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
PK Parameter, AUC0-4h of Carboplatin (Total Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-4h was defined as the area under the plasma concentration-time curve from time zero to 4h (determined as total platinum).
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
PK Parameter, Cmax of Carboplatin (Total Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed carboplatin plasma concentration (determined as total platinum)
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
PK Parameter, AUClast of Carboplatin (Total Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of carboplatin (determined as total platinum)
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
PK Parameter, Tmax of Carboplatin (Total Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum carboplatin plasma concentration (determined as total platinum). Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
PK Parameter, AUC0-4h of Carboplatin (Ultrafilterable Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-4h was defined as the area under the plasma concentration-time curve from time zero to 4h (determined as ultrafilterable platinum).
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
PK Parameter, Cmax of Carboplatin (Ultrafilterable Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed carboplatin plasma concentration (determined as ultrafilterable platinum)
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
PK Parameter, AUClast of Carboplatin (Ultrafilterable Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of carboplatin (determined as ultrafilterable platinum)
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
PK Parameter, Tmax of Carboplatin (Ultrafilterable Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum carboplatin plasma concentration (determined as ultrafilterable platinum). Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
Number of Participants With Anti-drug Antibodies (ADA) at Baseline for LAG525
Number of participants who had an ADA positive result at baseline for LAG525
Baseline
Number of Participants With Anti-drug Antibodies (ADA) on Treatment for LAG525
Number of participants who were treatment-induced ADA positive for LAG525 (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive for LAG525 (post-baseline ADA positive with titer that was at least the fold titer change greater than the ADA-positive baseline titer)
From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 3 years
Number of Participants With Anti-drug Antibodies (ADA) at Baseline for PDR001
Number of participants who had an ADA positive result at baseline for PDR001.
Baseline
Number of Participants With Anti-drug Antibodies (ADA) on Treatment for PDR001
Number of participants who were treatment-induced ADA positive for PDR001 (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive for PDR001 (post-baseline ADA positive with titer that was at least the fold titer change greater than the ADA-positive baseline titer)
From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 2.8 years
Fayetteville
Arkansas
72703
United States
Novartis Investigative Site
Caba
Buenos Aires
C1280AEB
Argentina
Novartis Investigative Site
Wooloongabba
Queensland
4102
Australia
Novartis Investigative Site
Melbourne
Victoria
3000
Australia
Novartis Investigative Site
Nedlands
Western Australia
6009
Australia
Novartis Investigative Site
Liège
4000
Belgium
Novartis Investigative Site
Montreal
Quebec
H3T 1E2
Canada
Novartis Investigative Site
Québec
G1S 4L8
Canada
Novartis Investigative Site
Paris
75231
France
Novartis Investigative Site
Lübeck
Schleswig-Holstein
23563
Germany
Novartis Investigative Site
Erlangen
91054
Germany
Novartis Investigative Site
Tübingen
72076
Germany
Novartis Investigative Site
Budapest
H 1122
Hungary
Novartis Investigative Site
Szeged
H-6720
Hungary
Novartis Investigative Site
Tel Aviv
6423906
Israel
Novartis Investigative Site
Naples
80131
Italy
Novartis Investigative Site
Nagoya
Aichi-ken
466 8560
Japan
Novartis Investigative Site
Nagoya
Aichi-ken
467-8602
Japan
Novartis Investigative Site
Yokohama
Kanagawa
241-8515
Japan
Novartis Investigative Site
Minato Ku
Tokyo
105-8470
Japan
Novartis Investigative Site
El Achrafiyé
166830
Lebanon
Novartis Investigative Site
El Metn
Lebanon
Novartis Investigative Site
Saida
652
Lebanon
Novartis Investigative Site
Singapore
169610
Singapore
Novartis Investigative Site
Seoul
Korea
05505
South Korea
Novartis Investigative Site
Seoul
03080
South Korea
Novartis Investigative Site
Seville
Andalusia
41013
Spain
Novartis Investigative Site
Madrid
28034
Spain
Novartis Investigative Site
Taipei
10002
Taiwan
Novartis Investigative Site
Taipei
11217
Taiwan
Novartis Investigative Site
Taipei
Taiwan
Novartis Investigative Site
Songkhla
90110
Thailand
FG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
FG00020 subjects
FG00134 subjects
FG00234 subjects
Treated
FG00019 subjects
FG00134 subjects
FG00234 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
NOT COMPLETED
FG00020 subjects
FG00134 subjects
FG00234 subjects
Type
Comment
Reasons
Adverse Event
FG0002 subjects
FG0013 subjects
FG0023 subjects
Death
FG0000 subjects
FG0010 subjects
FG0021 subjects
Physician Decision
FG0003 subjects
FG0016 subjects
FG0026 subjects
Progressive disease
FG00015 subjects
FG00123 subjects
FG00223 subjects
Patient decision
FG0000 subjects
FG0011 subjects
FG0021 subjects
Terminated by sponsor (end of study definition was met)
FG0000 subjects
FG0011 subjects
FG0020 subjects
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
BG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
BG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00020
BG00134
BG00234
BG00388
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
BG00053.8± 10.22
BG00150.9± 10.88
BG00253.3± 10.78
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00020
BG00134
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Asian
BG0008
BG0018
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
Overall Response Rate (ORR) Per Investigator's Assessment According to RECIST v1.1
Overall response rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 based on investigator's assessment. The 95% CIs were computed using two-sided exact binomial method.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.
Posted
Number
95% Confidence Interval
Percentage of participants
Up to approximately 14 months
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Units
Counts
Participants
OG00020
OG00134
OG00234
Title
Denominators
Categories
Title
Measurements
OG0005.0(0.1 to 24.9)
OG00132.4(17.4 to 50.5)
OG00217.6(6.8 to 34.5)
Secondary
Clinical Benefit Rate (CBR) Per Investigator's Assessment According to RECIST v1.1
CBR is defined as the percentage of participants with a best overall response (BOR) of confirmed CR or PR, or stable disease (SD) lasting 24 weeks or longer, according to RECIST 1.1 criteria. The 95% CI were computed using two-sided exact binomial method.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
FAS: All participants to whom study treatment was assigned by randomization.
Posted
Number
95% Confidence Interval
Percentage of Participants
Up to approximately 14 months
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Secondary
Duration of Response (DOR) Per Investigator's Assessment According to RECIST v1.1
DOR is the time between the first documented response (CR or PR) and the first documented progression or death due to underlying cancer based on RECIST1.1 and as per investigator's assessment. The DOR distribution was estimated using the Kaplan-Meier method and the 95% confidence intervals using the method of Brookmeyer and Crowley. If progression or death did not occur, the participant was censored at the date of last adequate tumor assessment.
CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Progression: at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. The sum must also demonstrate an absolute increase of at least 5 mm.
Participants with a confirmed CR or PR
Posted
Median
95% Confidence Interval
Months
From first documented response up to disease progression or death due to underlying cancer, whichever occurs first, up to approximately 14 months
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Secondary
Time to Response (TTR) Per Investigator's Assessment According to RECIST v1.1
TTR is the time from date of randomization to first documented response of CR or PR based on investigators' assessment and according to RECIST 1.1. Median TTR was summarized using descriptive statistics.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Participants with a confirmed CR or PR
Posted
Median
Full Range
Months
From date of randomization to first documented response (CR or PR), up to approximately 14 months
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Secondary
Progression Free Survival (PFS)
PFS is defined as time from date of randomization to the date of first documented progression or death due to any cause. PFS was assessed via investigator's assessment according to RECIST 1.1. PFS was censored at the date of the last adequate tumor assessment if no PFS event was observed prior to the analysis cut-off date or before the start of the new anticancer therapy date, whichever is earlier. The PFS distribution was estimated using the Kaplan-Meier method. The 95% confidence intervals were calculated using the method of Brookmeyer and Crowley.
FAS: All participants to whom study treatment was assigned by randomization.
Posted
Median
95% Confidence Interval
Months
From date of randomization to disease progression or death due to any cause, whichever occurs first, up to approximately 14 months
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Secondary
Overall Survival (OS)
OS is defined as the time from date of randomization to date of death due to any cause. If a participant was not known to have died, then OS was censored at the latest date the participant was known to be alive (on or before the cut-off date). The OS distribution was estimated using the Kaplan-Meier method. The 95% confidence intervals were calculated using the method of Brookmeyer and Crowley
FAS: All participants to whom study treatment was assigned by randomization.
Posted
Median
95% Confidence Interval
Months
From date of randomization to date of death due to any cause, up to 18 months
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Secondary
Pharmacokinetics (PK) Parameter, Area Under the Plasma Concentration Versus Time Curve From Time 0 to 504 Hours (AUC0-504h) of LAG525
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-504h was defined as the area under the plasma concentration-time curve from time zero to 504h.
LAG525 pharmacokinetic analysis set (PAS-LAG525) including all participants who provided at least one evaluable LAG525 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
day*microgram/miliLiter (day*ug/mL)
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Secondary
PK Parameter, Cmax of LAG525
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed plasma LAG525 concentration
PAS-LAG525 including all participants who provided at least one evaluable LAG525 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ug/mL
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Secondary
PK Parameter, AUClast of LAG525
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of LAG525
PAS-LAG525 including all participants who provided at least one evaluable LAG525 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
day*ug/mL
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Secondary
PK Parameter, Tmax of LAG525
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum LAG525 serum concentration. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
PAS-LAG525 including all participants who provided at least one evaluable LAG525 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
hr
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Secondary
PK Parameter, AUC0-504h of PDR001
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-504h was defined as the area under the plasma concentration-time curve from time zero to 504h.
PDR001 pharmacokinetic analysis set (PAS-PDR001) including all participants who provided at least one evaluable PDR001 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Mean
Standard Deviation
day*ug/mL
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
Units
Counts
Participants
Secondary
PK Parameter, Cmax of PDR001
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed PDR001 serum concentration
PAS-PDR001 including all participants who provided at least one evaluable PDR001 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ug/mL
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
Units
Counts
Participants
Secondary
PK Parameter, AUClast of PDR001
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of PDR001
PAS-PDR001 including all participants who provided at least one evaluable PDR001 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
day*ug/mL
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
Units
Counts
Participants
Secondary
PK Parameter, Tmax of PDR001
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum PDR001 serum concentration. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
PAS-PDR001 including all participants who provided at least one evaluable PDR001 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
hr
Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
Units
Counts
Secondary
PK Parameter, AUC0-4h of Carboplatin (Total Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-4h was defined as the area under the plasma concentration-time curve from time zero to 4h (determined as total platinum).
Carboplatin (plasma) PAS including all participants who provided at least one evaluable carboplatin PK plasma concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
hour*nanogram/miliLiter (hr*ng/mL)
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
ID
Title
Description
OG000
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG001
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Units
Counts
Secondary
PK Parameter, Cmax of Carboplatin (Total Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed carboplatin plasma concentration (determined as total platinum)
Carboplatin (plasma) PAS including all participants who provided at least one evaluable carboplatin PK plasma concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
ID
Title
Description
OG000
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG001
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Units
Counts
Participants
Secondary
PK Parameter, AUClast of Carboplatin (Total Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of carboplatin (determined as total platinum)
Carboplatin (plasma) PAS including all participants who provided at least one evaluable carboplatin PK plasma concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
ID
Title
Description
OG000
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG001
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Units
Counts
Secondary
PK Parameter, Tmax of Carboplatin (Total Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum carboplatin plasma concentration (determined as total platinum). Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Carboplatin (plasma) PAS including all participants who provided at least one evaluable carboplatin PK plasma concentration.Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
hr
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
ID
Title
Description
OG000
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG001
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Units
Counts
Secondary
PK Parameter, AUC0-4h of Carboplatin (Ultrafilterable Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-4h was defined as the area under the plasma concentration-time curve from time zero to 4h (determined as ultrafilterable platinum).
Carboplatin (plasma ultrafiltrate) PAS including all participants who provided at least one evaluable carboplatin PK plasma ultrafiltrate concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
hour*nanogram/miliLiter (hr*ng/mL)
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
ID
Title
Description
OG000
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG001
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Units
Secondary
PK Parameter, Cmax of Carboplatin (Ultrafilterable Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed carboplatin plasma concentration (determined as ultrafilterable platinum)
Carboplatin (plasma ultrafiltrate) PAS including all participants who provided at least one evaluable carboplatin PK plasma ultrafiltrate concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
ID
Title
Description
OG000
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG001
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Units
Counts
Secondary
PK Parameter, AUClast of Carboplatin (Ultrafilterable Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of carboplatin (determined as ultrafilterable platinum)
Carboplatin (plasma ultrafiltrate) PAS including all participants who provided at least one evaluable carboplatin PK plasma ultrafiltrate concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
ID
Title
Description
OG000
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG001
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Units
Secondary
PK Parameter, Tmax of Carboplatin (Ultrafilterable Platinum)
Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum carboplatin plasma concentration (determined as ultrafilterable platinum). Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Carboplatin (plasma ultrafiltrate) PAS including all participants who provided at least one evaluable carboplatin PK plasma ultrafiltrate concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
Posted
Geometric Mean
Geometric Coefficient of Variation
hr
Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days
ID
Title
Description
OG000
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG001
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Secondary
Number of Participants With Anti-drug Antibodies (ADA) at Baseline for LAG525
Number of participants who had an ADA positive result at baseline for LAG525
LAG525 Immunogenicity (IG) prevalence set: all participants in the FAS wo received at least one dose of LAG525 with a determinant baseline LAG525 IG sample or at least one determinant post-baseline LAG525 IG sample.
Posted
Count of Participants
Participants
No
Baseline
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Units
Counts
Participants
Secondary
Number of Participants With Anti-drug Antibodies (ADA) on Treatment for LAG525
Number of participants who were treatment-induced ADA positive for LAG525 (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive for LAG525 (post-baseline ADA positive with titer that was at least the fold titer change greater than the ADA-positive baseline titer)
LAG525 immunogenicity incidence set: all participants in the LAG525 immunogenicity prevalence set with a determinant LAG525 baseline IG sample and at least one determinant LAG525 post-baseline IG sample.
Posted
Count of Participants
Participants
No
From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 3 years
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Secondary
Number of Participants With Anti-drug Antibodies (ADA) at Baseline for PDR001
Number of participants who had an ADA positive result at baseline for PDR001.
PDR001 Immunogenicity (IG) prevalence set: all participants in the FAS who received at least one dose of PDR001 with a determinant baseline PDR001 IG sample or at least one determinant post-baseline PDR001 IG sample
Posted
Count of Participants
Participants
No
Baseline
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
Units
Counts
Participants
OG000
Secondary
Number of Participants With Anti-drug Antibodies (ADA) on Treatment for PDR001
Number of participants who were treatment-induced ADA positive for PDR001 (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive for PDR001 (post-baseline ADA positive with titer that was at least the fold titer change greater than the ADA-positive baseline titer)
PDR001 Immunogenicity incidence set: all subjects in the PDR001 Immunogenicity prevalence set with a determinant PDR001 baseline IG sample and at least one determinant PDR001 post-baseline IG sample.
Posted
Count of Participants
Participants
No
From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 2.8 years
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
Units
Counts
Participants
Post-Hoc
All Collected Deaths
On-treatment deaths were collected from first dose of study medication to 30 days after the last dose of study medication for a maximum duration of 2.9 years.
Extended safety follow up deaths were collected from day 31 post treatment up to 150 days post-treatment, for a maximum duration of 3.2 years.
Post-treatment deaths were collected after 150 days post-treatment, for a maximum duration of 3.2 years.
Safety set: all participants who received at least one dose of study treatment (i.e., at least one dose of any component of the study treatment, including incomplete infusion of spartalizumab, LAG525 or carboplatin).
Posted
Count of Participants
Participants
Up to 2.9 years (on-treatment), up to 3.2 years (extended safety follow-up and post-treatment)
ID
Title
Description
OG000
LAG525 + PDR001
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
OG001
LAG525+ PDR001+ Carboplatin
Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.
OG002
LAG525 + Carboplatin
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
Time Frame
In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to 2.9 years In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment, up to 3.2 years
Description
The safety analysis was performed in the safety set including all participants who received at least one dose of study treatment (i.e., at least one dose of any component of the study treatment, including incomplete infusion of spartalizumab, LAG525 or carboplatin).
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
LAG525 + PDR001 (On-treatment Period)
Participants received LAG525 and PDR001 administered as infusion once every 3 weeks
Participants received LAG525 and carboplatin administered as infusion once every 3 weeks
16
34
2
34
3
34
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG0030 affected34 at risk
EG0042 affected34 at risk
EG0051 affected34 at risk
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Myocarditis
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Wolff-Parkinson-White syndrome
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Fanconi syndrome
Congenital, familial and genetic disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Erosive duodenitis
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Faeces discoloured
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Intestinal ischaemia
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Disease progression
General disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
General physical health deterioration
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Pain
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Biliary colic
Hepatobiliary disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Pneumocystis jirovecii pneumonia
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Sepsis
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Septic shock
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Skin infection
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Subcutaneous abscess
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Thoracic vertebral fracture
Injury, poisoning and procedural complications
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Platelet count decreased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Troponin increased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Metastases to meninges
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Brain oedema
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Headache
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Renal tubular acidosis
Renal and urinary disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Pleuritic pain
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Atrial thrombosis
Cardiac disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Malaise
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG00220 affected34 at risk
EG0035 affected34 at risk
EG00419 affected34 at risk
EG0051 affected34 at risk
Leukopenia
Blood and lymphatic system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0023 affected34 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0029 affected34 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG00215 affected34 at risk
EG003
Goitre
Endocrine disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0025 affected34 at risk
EG003
Thyroiditis
Endocrine disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Dry eye
Eye disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0025 affected34 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0025 affected34 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0003 affected19 at risk
EG0010 affected19 at risk
EG0027 affected34 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0025 affected34 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0025 affected34 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0023 affected34 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0003 affected19 at risk
EG0010 affected19 at risk
EG00218 affected34 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0027 affected34 at risk
EG003
Asthenia
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG00211 affected34 at risk
EG003
Chest pain
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Chills
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Fatigue
General disorders
MedDRA (24.1)
Systematic Assessment
EG0002 affected19 at risk
EG0010 affected19 at risk
EG00211 affected34 at risk
EG003
Gait disturbance
General disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Induration
General disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Influenza like illness
General disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Malaise
General disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0023 affected34 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Oedema peripheral
General disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Pain
General disorders
MedDRA (24.1)
Systematic Assessment
EG0002 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Pyrexia
General disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0024 affected34 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Lymphangitis
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Rhinitis
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Skin infection
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0026 affected34 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0002 affected19 at risk
EG0010 affected19 at risk
EG0024 affected34 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0024 affected34 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Blood thyroid stimulating hormone increased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0024 affected34 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG00211 affected34 at risk
EG003
Platelet count decreased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG00214 affected34 at risk
EG003
SARS-CoV-2 test negative
Investigations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Weight decreased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0025 affected34 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (24.1)
Systematic Assessment
EG0002 affected19 at risk
EG0010 affected19 at risk
EG0024 affected34 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0024 affected34 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0024 affected34 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Hypophagia
Metabolism and nutrition disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0023 affected34 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0027 affected34 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0002 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0025 affected34 at risk
EG003
Metastases to skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (24.1)
Systematic Assessment
EG0002 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Headache
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0002 affected19 at risk
EG0010 affected19 at risk
EG0028 affected34 at risk
EG003
Intercostal neuralgia
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Peripheral sensory neuropathy
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Polyuria
Renal and urinary disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Breast pain
Reproductive system and breast disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Pelvic pain
Reproductive system and breast disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Vaginal discharge
Reproductive system and breast disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0002 affected19 at risk
EG0010 affected19 at risk
EG0027 affected34 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0024 affected34 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0024 affected34 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0021 affected34 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0000 affected19 at risk
EG0010 affected19 at risk
EG0023 affected34 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0003 affected19 at risk
EG0010 affected19 at risk
EG0023 affected34 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0002 affected19 at risk
EG0010 affected19 at risk
EG0024 affected34 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0002 affected19 at risk
EG0010 affected19 at risk
EG0026 affected34 at risk
EG003
Skin lesion
Skin and subcutaneous tissue disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0020 affected34 at risk
EG003
Hot flush
Vascular disorders
MedDRA (24.1)
Systematic Assessment
EG0001 affected19 at risk
EG0010 affected19 at risk
EG0022 affected34 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.