Sym015 (Anti-MET) in Patients With Advanced Solid Tumor M... | NCT02648724 | Trialant
NCT02648724
Sponsor
Symphogen A/S
Status
Completed
Last Update Posted
Jun 22, 2022Actual
Enrollment
57Actual
Phase
Phase 1Phase 2
Conditions
Oncology
MET Gene Amplification
NSCLC
MET Gene Mutation
Non Small Cell Lung Cancer
Interventions
Sym015
Countries
United States
Denmark
Hong Kong
South Korea
Spain
Taiwan
Protocol Section
Identification Module
NCT ID
NCT02648724
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
Sym015-01
Secondary IDs
ID
Type
Description
Link
2016-003912-11
EudraCT Number
Brief Title
Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies
Official Title
An Open-Label, Multicenter Phase 1a/2a Trial Investigating the Safety, Tolerability and Antitumor Activity of Multiple Doses of Sym015, a Monoclonal Antibody Mixture Targeting MET, in Patients With Advanced Solid Tumor Malignancies
Acronym
Not provided
Organization
Symphogen A/SINDUSTRY
Status Module
Record Verification Date
Apr 2022
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
Mar 2016Actual
Primary Completion Date
Dec 2020Actual
Completion Date
Dec 2020Actual
First Submitted Date
Jan 4, 2016
First Submission Date that Met QC Criteria
Jan 5, 2016
First Posted Date
Jan 7, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Dec 21, 2021
Results First Submitted that Met QC Criteria
May 24, 2022
Results First Posted Date
Jun 22, 2022Actual
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
May 24, 2022
Last Update Posted Date
Jun 22, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Symphogen A/SINDUSTRY
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
This is the first study to test Sym015 in humans. The primary purpose of this study is to see if Sym015 is safe and effective for patients with advanced solid tumor malignancies without available therapeutic options.
Detailed Description
In the first part of the study (Part 1, dose-escalation), Sym015 was evaluated for safety and tolerability. Additionally, the recommended Phase 2 dose (RP2D) was to be determined. Sym015 was given at different dose levels on an every second week (Q2W) dosing schedule. Each patient was given one single weight based dose level.
In the second part of the study (Part 2, dose-expansion), dosing was to be at the RP2D on a Q2W dosing schedule. Three cohorts were included:
Basket Cohort: Patients with KRAS wild-type (WT) advanced solid tumor malignancies with MET-amplification and without therapeutic options. Patients must have no prior therapy with MET-targeting agents, except a subset of patients having received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI). As of December 2018, accrual to this cohort was suspended.
Non-Small Cell Lung Carcinoma (NSCLC) MET-Amplified Cohort: Patients with advanced NSCLC with MET-amplification, and without available therapeutic options. Patients may have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.
NSCLC with MET exon 14 skipping alteration (METex14del) Cohort: Patients with advanced NSCLC METex14del, and without therapeutic options. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Conditions Module
Conditions
Oncology
MET Gene Amplification
NSCLC
MET Gene Mutation
Non Small Cell Lung Cancer
Keywords
Advanced Solid Tumor Malignancies
MET Gene Amplification
MET Amplification
Wild-type
NSCLC
METex14del
Non-Small Cell Lung Carcinoma
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 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
57Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part 1: 6 mg/kg
Experimental
Sym015 was tested in four dose titration cohorts. Patients in this cohort received 6 mg/kg. A substitute or an additional dose level could potentially be evaluated.
Drug: Sym015
Part 1: 12 mg/kg
Experimental
Sym015 was tested in four dose titration cohorts. Patients in this cohort received 12 mg/kg. A substitute or an additional dose level could potentially be evaluated.
Drug: Sym015
Part 1: 18 mg/kg
Experimental
Sym015 was tested in four dose titration cohorts. Patients in this cohort received 18 mg/kg. A substitute or an additional dose level could potentially be evaluated.
Drug: Sym015
Part 1: 24 mg/kg
Experimental
Sym015 was tested in four dose titration cohorts. Patients in this cohort received 24 mg/kg. A substitute or an additional dose level could potentially be evaluated.
Drug: Sym015
Part 2: Basket Cohort
Experimental
Patients with KRAS WT advanced solid tumor malignancies with MET-amplification were to receive Sym015 at the RP2D. Included in this group was a subset of patients who have received prior therapy with a MET-targeting TKI.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Sym015
Drug
Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
Part 1: 12 mg/kg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration
The primary objective of Part 1 was to assess the safety and tolerability of Sym015 on a Q2W schedule. This was assessed by evaluating the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym015 administration. Q2W = every second week.
Cycle 1, the initial 28-day period of Q2W dosing
Part 2: Documented, Confirmed Objective Response (OR)
The primary objective of Part 2 was to evaluate the antitumor activity of Sym015 when administered at the Q2W RP2D to patients in the different cohorts. Documented OR was defined as partial response [PR] or complete response [CR]) as assessed by CT or MRI using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; CR = Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
Q2W = every second week. RP2D = recommended phase 2 dose.
24 months
Secondary Outcomes
Measure
Description
Time Frame
Part 1: Determine a Q2W RP2D of Sym015.
Determination based on an evaluation of the patient data for DLTs from Part 1. Q2W = every second week. RP2D = recommended phase 2 dose.
12 Months
Immunogenicity of Sym015: Part 1.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Life expectancy >3 months assessed during Screening.
Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic, and that is refractory to standard therapy or for which no standard therapy is available or accessible.
If female and of childbearing potential: a negative pregnancy test.
Male or female: either not of childbearing potential or agreeing to use a medically effective method of contraception as per institutional standards during the trial and for 4 months after the last dose of trial drug.
Part 1 ONLY: Tumor documented to be KRAS WT by local assessment.
Part 2 ONLY:
Measurable disease according to RECIST v1.1 that has been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to Cycle 1/Day 1 (C1/D1).
Basket Cohort ONLY:
Tumor documented to be KRAS WT by local assessment according to institutional standards. If KRAS WT is not previously documented and if archival tissue is not available for pretrial assessment, patient must be willing to undergo a tumor biopsy to confirm eligibility.
Confirmed MET-amplification by local assessment.
No prior therapy with MET-targeting agents (except a subset of patients having received prior therapy with a MET-targeting TKI).
Willingness to undergo a pre- and post-dosing biopsy (maximum of 2 biopsies) from primary or metastatic tumor site(s) considered safely accessible for biopsy
NSCLC MET-Amplified Cohort ONLY:
Documented NSCLC meeting disease criteria as defined per protocol.
Documented MET-amplification.
May have received prior therapy with MET-targeting and/or EGFR-targeting agents (antibodies or TKIs).
Willingness to undergo a pre-dosing biopsy (mandatory unless a recent tumor biopsy is available), and potentially a biopsy at the End of Cycle 2 (EOC2) (optional), from a primary or metastatic tumor site considered safely accessible for biopsy.
NSCLC METex14del Cohort ONLY:
Documented NSCLC meeting disease criteria as defined per protocol.
Documented METex14del (tumors need not be MET-amplified).
May have received prior therapy with MET-targeting and/or EGFR-targeting agents (antibodies or TKIs).
Willingness to undergo a pre-dosing biopsy (mandatory unless a recent tumor biopsy is available), and potentially a biopsy at the EOC2 (optional), from a primary or metastatic tumor site considered safely accessible for biopsy.
Exclusion Criteria:
Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to C1/D1, except nitrosoureas and mitomycin C within 6 weeks prior to C1/D1.
Immunosuppressive or systemic hormonal therapy within 2 weeks prior to C1/D1, with exceptions.
Use of hematopoietic growth factors within 2 weeks prior to C1/D1.
Active second malignancy or history of another malignancy within the last 3 years, with exceptions.
Central nervous system (CNS) malignancy including primary malignancies of the CNS and known, untreated CNS or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS involvement for which treatment is required.
Inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy.
Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any prior surgical procedure.
Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 1 month prior to C1/D1, unless adequately treated and stable.
Active uncontrolled bleeding or a known bleeding diathesis.
Significant cardiovascular disease or condition.
Abnormal hematologic, renal or hepatic function.
Part 2 ONLY:
Radiotherapy against target lesions within 4 weeks prior to C1/D1, unless there is documented progression of the lesion following the radiotherapy.
Basket Cohort ONLY:
Prior therapy with MET-inhibiting agents (exceptions will be a subset of patients that will be entered to the Basket Cohort after having received prior therapy with a MET-targeting TKI).
Prior therapy with antibody to hepatocyte growth factor (HGF).
Basket Cohort and NSCLC MET-Amplified Cohort ONLY:
Tumor status demonstrating MET-polysomy in the absence of MET-amplification, as specified per protocol. Patients in the NSCLC METex14del Cohort with polysomy are eligible.
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
Amita Patnaik, MD, FRCP(C)
South Texas Accelerated Research Therapeutics, LLC
Grandal MM, Havrylov S, Poulsen TT, Koefoed K, Dahlman A, Galler GR, Conrotto P, Collins S, Eriksen KW, Kaufman D, Woude GFV, Jacobsen HJ, Horak ID, Kragh M, Lantto J, Bouquin T, Park M, Pedersen MW. Simultaneous Targeting of Two Distinct Epitopes on MET Effectively Inhibits MET- and HGF-Driven Tumor Growth by Multiple Mechanisms. Mol Cancer Ther. 2017 Dec;16(12):2780-2791. doi: 10.1158/1535-7163.MCT-17-0374. Epub 2017 Aug 11.
See Also Links
Not provided
Available IPD Information
Not provided
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
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part 1: Dose-Escalation; Period 1: 6 mg/kg
Patients received 6 mg/kg Symp015.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
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
Dec 7, 2018
Dec 21, 2021
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
No data available
No data is available for this block.
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Arms 1-4 comprises part 1 (dose-escalation), which is an as evaluation of 4 different dose levels (DL), 6, 12, 18, and 24 mg/kg. DL data from part 1 is presented as merged in the other sections. This is due to that there were no dose level toxicities reported during the study.
Arms 5-7 comprises part 2 (dose-expansion).
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
Drug: Sym015
Part 2: NSCLC MET-Amplified Cohort
Experimental
Patients with advanced NSCLC with MET-amplification were to receive Sym015 at the RP2D. Patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Drug: Sym015
Part 2: NSCLC METex14del Cohort
Experimental
Patients with advanced NSCLC with METex14del were to receive Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. mutation.
Drug: Sym015
Part 1: 18 mg/kg
Part 1: 24 mg/kg
Part 1: 6 mg/kg
Part 2: Basket Cohort
Part 2: NSCLC MET-Amplified Cohort
Part 2: NSCLC METex14del Cohort
Anti-MET
Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
Cycle 1: Day (D) 1, Cycle 3, 5, 7: D1 (+-2), End of treatment: At or by D10, Follow-up: 1 month after last dose of study treatment (30+7D)
Immunogenicity of Sym015: Part 2.
Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
Cycle 1: Day (D) 1, Cycle 2, 3, 5, 7: D1 (+-2), End of treatment: At or by D10, Follow-up: 1 month after last dose of study treatment (30+7D)
Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose
Estimated using non-compartmental methods and actual time points following the first dose of Sym015.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 2: Area Under the Concentration-time Curve in a Dosing Interval (AUC)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 1: Cmax
Maximum serum concentration was derived from observed data.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 2: Cmax
Maximum serum concentration was derived from observed data following the first dose of Sym015 for the full basket cohort.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 1: Time to Reach Maximum Concentration (Tmax)
Time to reach maximum concentration (Tmax) was derived from observed data.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 2: Time to Reach Maximum Concentration (Tmax)
Time to reach maximum concentration (Tmax) was derived from observed data following the first dose of Sym015 for the full basket cohort.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 1: Trough Concentration (Ctrough)
Ctrough was derived from observed data.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 2: Trough Concentration (Ctrough)
Ctrough was derived from observed data following the first dose of Sym015 for the whole basket cohort.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 1: Elimination Half-life (T½)
Estimated using non-compartmental methods and actual time points.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 2: Elimination Half-life (T½)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 1: Clearance (CL)
Estimated using non-compartmental methods and actual time points.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 2: Clearance (CL)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
Part 2: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by OR.
This applies to the subset of patients in the Basket Cohort who received prior therapy with a MET-targeting TKI. Documented OR (defined as PR or CR), assessed by RECIST v1.1 at any time during trial participation by Investigator assessment.
Objective Response (OR) is presented. Documented OR was defined as partial response [PR] or complete response [CR]) as assessed by CT or MRI using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment.
PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; CR = Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
24 Months
Part 2: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by DCR.
This applies to the subset of patients in the Basket Cohort who received prior therapy with a MET-targeting TKI. Documented OR (defined as PR or CR), assessed by RECIST v1.1 at any time during trial participation by Investigator assessment.
Disease control rate (DCR) is presented. The DCR was defined as the percentage of patients who had BOR of confirmed CR or confirmed PR or SD (including unconfirmed CR/PR, provided 6 weeks minimum criteria for SD duration was met).
BOR = Best Overall Response. CR = Complete Response. PR = Partial Response. SD = Stable Disease.
24 Months
Chicago
Illinois
60637
United States
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis
Indiana
46202
United States
Massachusetts General Hospital
Boston
Massachusetts
02114
United States
Dana Farber Cancer Institute/D -1251
Boston
Massachusetts
02215
United States
Comprehensive Cancer Centers of Nevada
Las Vegas
Nevada
89169
United States
University Hospitals Cleveland Medical Center
Cleveland
Ohio
44106
United States
University of Texas Southwestern Medical Center
Dallas
Texas
75390
United States
The University of Texas M.D. Anderson Cancer Center
Houston
Texas
77030
United States
South Texas Accelerated Research Therapeutics, LLC
San Antonio
Texas
78229
United States
Rigshospitalet
Copenhagen
2100
Denmark
Queen Mary Hospital
Hong Kong
Hong Kong
CHA Bundang Medical Center, CHA University
Seongnam-si
Gyeonggi-do
13496
South Korea
Severance Hospital, Yonsei University Health System
Seoul
03722
South Korea
Asan Medical Center
Seoul
05505
South Korea
Gangnam Severance Hospital, Yonsei University Health System
Seoul
06273
South Korea
Samsung Medical Center
Seoul
06351
South Korea
Korea University Guro Hospital
Seoul
08308
South Korea
Hospital Universitario Quiron Dexeus
Barcelona
Barcelona/Cataluna
08028
Spain
Hospital Universitario Vall d'Hebron
Barcelona
Barcelona/Cataluna
08035
Spain
Hospital Clinic de Barcelona
Barcelona
Barcelona/Cataluna
08036
Spain
Centro Oncologico MD Anderson
Madrid
28033
Spain
China Medical University Hospital
Taichung
40447
Taiwan
Taichung Veterans General Hospital
Taichung
40705
Taiwan
National Cheng Kung University Hospital
Tainan
70403
Taiwan
Taipei Medical University Hospital
Taipei
11031
Taiwan
Tri-Service General Hospital
Taipei
11490
Taiwan
FG001
Part 1: Dose-Escalation; Period 2: 12mg/kg
Patients received 12 mg/kg Symp015.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
FG002
Part 1: Dose-Escalation; Period 3:18mg/kg
Patients received 18 mg/kg Symp015.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
FG003
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-.
Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
FG004
Part 2: Dose-Expansion, Basket Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
Basket Cohort:
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
FG005
Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC MET-Amplified Cohort:
Patients with advanced NSCLC with MET-amplification were to receive Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
FG006
Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC METex14del Cohort:
Patients with advanced NSCLC with METex14del were to receive Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. mutation.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
FG0003 subjects
FG0013 subjects
FG0023 subjects
FG0033 subjects
FG00425 subjects
FG0058 subjects
FG00612 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
NOT COMPLETED
FG0003 subjects
FG0013 subjects
FG0023 subjects
FG0033 subjects
FG00425 subjects
FG0058 subjects
FG00612 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
FG0060 subjects
Progressive disease
FG0002 subjects
FG0012 subjects
FG0022 subjects
FG0033 subjects
FG004
Other reason (unknown)
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Transferred to named patient program
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1: Dose-Escalation, 6 mg/kg
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
BG001
Part 1: Dose-Escalation, 12 mg/kg
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
BG002
Part 1: Dose-Escalation 18 mg/kg
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
BG003
Part 1: Dose-Escalation 24 mg/kg
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
BG004
Part 2: Dose-Expansion, Basket Cohort
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
BG005
Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort
Patients with advanced NSCLC with MET-amplification received Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
BG006
Part 2: Dose-Expansion, NSCLC METex14del Cohort
Patients with advanced NSCLC with METex14del received Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
BG007
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0003
BG0013
BG0023
BG0033
BG00425
BG0058
BG00612
BG00757
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
BG00055.7± 14.57
BG00162.0± 11.79
BG00255.3± 11.24
BG003
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
18-65 years
Title
Measurements
BG0002
BG0011
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0001
BG0012
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
South Korea
Title
Measurements
BG0000
BG0010
BG002
Body weight
Mean
Standard Deviation
kg
Title
Denominators
Categories
Title
Measurements
BG00082.2± 17.86
BG00162.5± 12.03
BG002
Body mass index (BMI)
BMI was not evaluable for all participants
Mean
Standard Deviation
kg per square meter
Title
Denominators
Categories
Title
Measurements
BG00028.10± 1.132
BG00123.65± 3.978
ECOG-PS
ECOG-PS=Eastern Cooperative Oncology Group performance status. It describes patient functioning level on a 5 graded scale.
Grade 0: Fully active, able to carry on all pre-disease performance without restriction Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours Grade 3-5: Ranges from capable of only limited selfcare to dead.
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
0
BG0001
BG001
Site of primary tumor
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Breast
BG0000
BG0010
BG002
Histopathologic diagnosis
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Adenocarcinoma
BG0003
BG0011
BG002
Anatomic based cancer type
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Adenocarcinoma of Parotid Gland
BG0000
BG0010
BG002
Time since initial diagnosis
Data were not available for all patients in Part 2
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG0004.7± 2.52
BG0012.3± 1.53
Previous debulking surgery
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
No
BG0003
BG0011
BG002
Sites with metastasis
Count of Participants
Participants
Title
Denominators
Categories
Abdomen, pelvis
Title
Measurements
BG0001
BG0010
BG002
Number of sites with metastasis
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
0
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
Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration
The primary objective of Part 1 was to assess the safety and tolerability of Sym015 on a Q2W schedule. This was assessed by evaluating the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym015 administration. Q2W = every second week.
For evaluation of DLTs, the DLT analysis set was used. This comprised all patients enrolled in Part 1 who had received at least one dose of Sym015, except patients who did not complete Cycle 1 (i.e., the initial 28-day period of Q2W dosing) for reasons other than drug toxicity.
Posted
Number
Number of DLTs
Cycle 1, the initial 28-day period of Q2W dosing
ID
Title
Description
OG000
Part 1: Dose-Escalation; Period 1, 6 mg/kg
Patients received 6 mg/kg Sym015.
Sym015 was tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
OG001
Part 1: Dose-Escalation; Period 2: 12mg/kg
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET
OG002
Part 1: Dose-Escalation; Period 3:18mg/kg
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
OG003
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Part 2: Documented, Confirmed Objective Response (OR)
The primary objective of Part 2 was to evaluate the antitumor activity of Sym015 when administered at the Q2W RP2D to patients in the different cohorts. Documented OR was defined as partial response [PR] or complete response [CR]) as assessed by CT or MRI using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; CR = Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
Q2W = every second week. RP2D = recommended phase 2 dose.
The Full Analysis Set (FAS) comprised all enrolled patients who had received at least one dose of Sym015.
Posted
Count of Participants
Participants
24 months
ID
Title
Description
OG000
Part 2: Basket Cohort
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
OG001
Part 2: Patients in NSCLC MET-Amplified Cohort
Secondary
Part 1: Determine a Q2W RP2D of Sym015.
Determination based on an evaluation of the patient data for DLTs from Part 1. Q2W = every second week. RP2D = recommended phase 2 dose.
It was not possible to determine this endpoint as no DLTs were observed. The RP2D combination was not established and was instead chosen based on other safety findings as well as pharmacokinetic data, as described in the protocol.
Posted
Number
mg/kg
12 Months
ID
Title
Description
OG000
Part 1: Dose-Escalation (4 Arms Combined)
Sym015 was tested in four dose titration cohorts (6, 12, 18 and 24 mg/kg) with 3 patients per dose level. A substitute or an additional dose level could potentially be evaluated.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
Units
Counts
Participants
OG000
Secondary
Immunogenicity of Sym015: Part 1.
Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
The Full Analysis Set (FAS) comprised all enrolled patients who had received at least one dose of Sym015.
Posted
Count of Participants
Participants
Cycle 1: Day (D) 1, Cycle 3, 5, 7: D1 (+-2), End of treatment: At or by D10, Follow-up: 1 month after last dose of study treatment (30+7D)
ID
Title
Description
OG000
6 mg/kg
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG001
12 mg/kg
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG002
18 mg/kg
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG003
24 mg/kg
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Secondary
Immunogenicity of Sym015: Part 2.
Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
The Full Analysis Set (FAS) comprised all enrolled patients who had received at least one dose of Sym015.
Posted
Count of Participants
Participants
Cycle 1: Day (D) 1, Cycle 2, 3, 5, 7: D1 (+-2), End of treatment: At or by D10, Follow-up: 1 month after last dose of study treatment (30+7D)
ID
Title
Description
OG000
Part 2: Basket Cohort
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
OG001
Part 2: Patients in NSCLC MET-Amplified Cohort
Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.
NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.
OG002
Part 2: Patients in NSCLC METEx14Del Cohort
Secondary
Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose
Estimated using non-compartmental methods and actual time points following the first dose of Sym015.
Posted
Median
Full Range
h*μg/mL
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
6 mg/kg
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG001
12 mg/kg
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG002
18 mg/kg
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG003
24 mg/kg
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Secondary
Part 2: Area Under the Concentration-time Curve in a Dosing Interval (AUC)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Posted
Median
Full Range
h*ug/mL
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
Part 2 (Dose Expansion): Basket Cohort
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
OG001
Part 2 (Dose Expansion): Patients in NSCLC MET-Amplified Cohort
Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.
OG002
Part 2 (Dose Expansion): Patients in NSCLC METEx14Del Cohort
Secondary
Part 1: Cmax
Maximum serum concentration was derived from observed data.
Posted
Median
Full Range
ug/mL
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
6 mg/kg
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG001
12 mg/kg
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG002
18 mg/kg
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG003
24 mg/kg
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Secondary
Part 2: Cmax
Maximum serum concentration was derived from observed data following the first dose of Sym015 for the full basket cohort.
Posted
Median
Full Range
ug/mL
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
Part 2 (Dose-Expansion): Basket Cohort
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
OG001
Part 2 (Dose-Expansion): Patients in NSCLC MET-Amplified Cohort
Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.
OG002
Part 2 (Dose-Expansion): Patients in NSCLC METEx14Del Cohort
Secondary
Part 1: Time to Reach Maximum Concentration (Tmax)
Time to reach maximum concentration (Tmax) was derived from observed data.
Posted
Median
Full Range
hours
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
6 mg/kg
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG001
12 mg/kg
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG002
18 mg/kg
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG003
24 mg/kg
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Secondary
Part 2: Time to Reach Maximum Concentration (Tmax)
Time to reach maximum concentration (Tmax) was derived from observed data following the first dose of Sym015 for the full basket cohort.
Posted
Median
Full Range
hours
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
Part 2 (Dose-Expansion): Basket Cohort
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
OG001
Part 2 (Dose-Expansion): Patients in NSCLC MET-Amplified Cohort
Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.
Secondary
Part 1: Trough Concentration (Ctrough)
Ctrough was derived from observed data.
Posted
Median
Full Range
μg/mL
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
6 mg/kg
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG001
12 mg/kg
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG002
18 mg/kg
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG003
24 mg/kg
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Secondary
Part 2: Trough Concentration (Ctrough)
Ctrough was derived from observed data following the first dose of Sym015 for the whole basket cohort.
Posted
Median
Full Range
μg/mL
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
Part 2 (Dose-Expansion): Basket Cohort
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
OG001
Part 2 (Dose-Expansion): Patients in NSCLC MET-Amplified Cohort
Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.
OG002
Part 2 (Dose-Expansion): Patients in NSCLC METEx14Del Cohort
Secondary
Part 1: Elimination Half-life (T½)
Estimated using non-compartmental methods and actual time points.
Numbers reflects evaluable participants. Evaluable participants = T½ is only reported if at least three data points were available in the terminal phase, R2 in 0.85 or above and the time span between the first and the last data point for z covers at least 1.5 half-lives. Reference: V-QUAL-107812
Posted
Median
Full Range
hours
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
6 mg/kg
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG001
12 mg/kg
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG002
18 mg/kg
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG003
24 mg/kg
Secondary
Part 2: Elimination Half-life (T½)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Posted
Median
Full Range
hours
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
Part 2 (Dose-Expansion): Basket Cohort
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
OG001
Part 2 (Dose-Expansion): Patients in NSCLC MET-Amplified Cohort
Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.
OG002
Part 2 (Dose-Expansion): Patients in NSCLC METEx14Del Cohort
Secondary
Part 1: Clearance (CL)
Estimated using non-compartmental methods and actual time points.
Samples were determined for subjects in the 6 and 12 mg/kg cohorts. No samples from subjects in the 18 and 24 mg/kg cohorts were available for analysis.
Posted
Median
Full Range
mL/h
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
6 mg/kg
Cohort of subjects receiving a dose of 6 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG001
12 mg/kg
Cohort of subjects receiving a dose of 12 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG002
18 mg/kg
Cohort of subjects receiving a dose of 18 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
OG003
24 mg/kg
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Secondary
Part 2: Clearance (CL)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Posted
Median
Full Range
mL/h/kg
From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.
ID
Title
Description
OG000
Part 2 (Dose-Expansion): Basket Cohort
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
OG001
Part 2 (Dose-Expansion): Patients in NSCLC MET-Amplified Cohort
Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.
OG002
Secondary
Part 2: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by OR.
This applies to the subset of patients in the Basket Cohort who received prior therapy with a MET-targeting TKI. Documented OR (defined as PR or CR), assessed by RECIST v1.1 at any time during trial participation by Investigator assessment.
Objective Response (OR) is presented. Documented OR was defined as partial response [PR] or complete response [CR]) as assessed by CT or MRI using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment.
PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; CR = Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
Posted
Count of Participants
Participants
24 Months
ID
Title
Description
OG000
Patients With Prior MET-targeting TKI Therapy (Basket Cohort)
Patients in Basket Cohort, with prior MET-targeting TKI therapy. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor. TKI = tyrosine kinase inhibitor.
OG001
Patients Without Prior MET-targeting TKI Therapy (Basket Cohort)
Patients in Basket Cohort, without prior MET-targeting TKI therapy. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor. TKI = tyrosine kinase inhibitor.
Secondary
Part 2: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by DCR.
This applies to the subset of patients in the Basket Cohort who received prior therapy with a MET-targeting TKI. Documented OR (defined as PR or CR), assessed by RECIST v1.1 at any time during trial participation by Investigator assessment.
Disease control rate (DCR) is presented. The DCR was defined as the percentage of patients who had BOR of confirmed CR or confirmed PR or SD (including unconfirmed CR/PR, provided 6 weeks minimum criteria for SD duration was met).
BOR = Best Overall Response. CR = Complete Response. PR = Partial Response. SD = Stable Disease.
Posted
Count of Participants
Participants
24 Months
ID
Title
Description
OG000
Patients With Prior MET-targeting TKI Therapy (Basket Cohort)
Patients in Basket Cohort, with prior MET-targeting TKI therapy. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor. TKI = tyrosine kinase inhibitor.
OG001
Patients Without Prior MET-targeting TKI Therapy (Basket Cohort)
Patients in Basket Cohort, without prior MET-targeting TKI therapy. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor. TKI = tyrosine kinase inhibitor.
Time Frame
24 months
Description
Not provided
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
Part 1: Dose-Escalation; Period 1: 6 mg/kg
Patients received 6 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
0
3
1
3
2
3
EG001
Part 1: Dose-Escalation; Period 2: 12mg/kg
Patients received 12 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
0
3
1
3
3
3
EG002
Part 1: Dose-Escalation; Period 3:18mg/kg
Patients received 18 mg/kg Symp015. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
0
3
0
3
3
3
EG003
Part 1: Dose-Escalation; Period 4: 24 mg/kg
Patients received 24 mg/kg Symp015-. Sym015 was tested in four dose titration cohorts. Patients received increasing doses of 6, 12, 18 and 24 mg/kg every second week (Q2W). A substitute or an additional dose level could potentially be evaluated.
Dose-escalation followed a standard 3+3 design with escalation dependent upon the occurrence of dose level toxicity.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
0
3
1
3
3
3
EG004
Part 2: Dose-Expansion, Basket Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
Basket Cohort:
Patients with KRAS proto-oncogene wild-type (KRAS WT) advanced solid tumor malignancies with MET-amplification received Sym015 at the recommended Phase 2 dose. Included in this group was a subset of patients who received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI).
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
0
25
8
25
23
25
EG005
Part 2: Dose-Expansion, NSCLC MET-Amplified Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC MET-Amplified Cohort:
Patients with advanced NSCLC with MET-amplification were to receive Sym015 at the RP2D. Patients may have received prior therapy with METtargeting and/or EGFR-targeting agents.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
0
8
4
8
8
8
EG006
Part 2: Dose-Expansion, NSCLC METEx14Del Cohort
During Part 2, three Cohorts received Sym015 at the recommended phase 2 dose on a every second week dosing schedule:
NSCLC METex14del Cohort:
Patients with advanced NSCLC with METex14del were to receive Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. mutation.
Sym015: Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
3
12
6
12
12
12
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Pelvic abscess
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG0030 events0 affected3 at risk
EG0040 events0 affected25 at risk
EG0050 events0 affected8 at risk
EG0060 events0 affected12 at risk
Intra-abdominal fluid collection
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Bacteraemia
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Bone abscess
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Septic shock
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Rectal hemorrhage
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Small intestinal perforation
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Hyperkalemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Hypoalbuminemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Generalized edema
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Edema peripheral
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Hepatitis
Hepatobiliary disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Peripheral ischemia
Vascular disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Nausea
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG0030 events0 affected3 at risk
EG0046 events6 affected25 at risk
EG0052 events2 affected8 at risk
EG0062 events2 affected12 at risk
Constipation
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0002 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0012 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Diarrhea
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0002 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Presbyesophagus
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Salivary gland enlargement
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Edema peripheral
General disorders
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0013 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Fatigue
General disorders
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0011 events1 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Pyrexia
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Asthenia
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Early satiety
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Facial pain
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Feeling abnormal
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pain
General disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Hypoalbuminemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Hypokalemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0002 events2 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Hypomagnesemia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Hyponatremia
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Weight decreased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Dyspnea
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Respiratory tract congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Headache
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Cognitive disorder
Nervous system disorders
MedDRA (23.1)
Systematic Assessment
EG0001 events1 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Anemia
Blood and lymphatic system disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Cystitis
Infections and infestations
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0013 events2 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Ear discomfort
Ear and labyrinth disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Ear hemorrhage
Ear and labyrinth disorders
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA (23.1)
Systematic Assessment
EG0000 events0 affected3 at risk
EG0010 events0 affected3 at risk
EG0022 events2 affected3 at risk
EG003
Tumor pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Abdominal cavity, diaphragm, subcutis, para- renal mass, Sub-Hepatic Mass
Title
Measurements
BG0000
BG0010
BG0021
BG0030
BG0040
BG0050
BG0060
BG0071
Adrenal gland
Title
Measurements
BG0000
BG0010
BG0021
BG0030
BG0044
BG0051
BG0064
BG00710
Bone
Title
Measurements
BG0001
BG0010
BG0022
BG0032
BG0046
BG0052
BG0067
BG00720
Both ovaries, peritoneum, colon
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0041
BG0050
BG0060
BG0071
Brain
Title
Measurements
BG0000
BG0010
BG0021
BG0030
BG0041
BG0052
BG0061
BG0075
Duodenum
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0041
BG0050
BG0060
BG0071
Effusion
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0041
BG0050
BG0060
BG0071
Kidney
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0062
BG0072
Liver
Title
Measurements
BG0002
BG0012
BG0020
BG0032
BG0048
BG0051
BG0062
BG00717
Lungs
Title
Measurements
BG0001
BG0012
BG0022
BG0032
BG0048
BG0057
BG0069
BG00731
Lymph nodes
Title
Measurements
BG0002
BG0013
BG0020
BG0033
BG00420
BG0056
BG0067
BG00741
Lymph nodes and Lymphangitis Carcinomatoses
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
BG0051
BG0060
BG0071
Muscle
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0061
BG0071
Pelvis, abdominal wall, spleen
Title
Measurements
BG0000
BG0011
BG0020
BG0030
BG0040
BG0050
BG0060
BG0071
Peritoneal
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0042
BG0050
BG0060
BG0072
Peritoneum, peribiliary
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0041
BG0050
BG0060
BG0071
Pleura
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0062
BG0072
Pleural based metastases
Title
Measurements
BG0000
BG0011
BG0020
BG0030
BG0040
BG0050
BG0060
BG0071
Primary gastric cancer
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0041
BG0050
BG0060
BG0071
Rectum
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0041
BG0050
BG0060
BG0071
Skin
Title
Measurements
BG0000
BG0010
BG0021
BG0030
BG0040
BG0050
BG0061
BG0072
Soft tissue
Title
Measurements
BG0000
BG0011
BG0021
BG0031
BG0042
BG0050
BG0063
BG0078
Spleen, pelvis, abdomen, left ovary
Title
Measurements
BG0001
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0071
Subpleura
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
BG0051
BG0060
BG0071
Thyroid gland
Title
Measurements
BG0000
BG0010
BG0020
BG0031
BG0040
BG0050
BG0060
BG0071
0
BG0030
BG0040
BG0050
BG0060
BG0070
1
BG0001
BG0010
BG0021
BG0030
BG0047
BG0052
BG0061
BG00712
2
BG0001
BG0010
BG0020
BG0030
BG0048
BG0051
BG0063
BG00713
3
BG0000
BG0012
BG0021
BG0031
BG0046
BG0053
BG0064
BG00717
More than 3
BG0001
BG0011
BG0021
BG0032
BG0044
BG0052
BG0064
BG00715
3
0
Patients had MET-amplified advanced NSCLC without available therapeutic options. Patients could have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.
NSCL = non-small cell lung cancer. MET = MET proto-oncogene tyrosine kinase, hepatocyte growth factor receptor.
OG002
Part 2: Patients in NSCLC METEx14Del Cohort
Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. NSCLC = non-small cell lung cancer. METEx14Del = MET exon 14 skipping alteration. EGFR = epidermal growth factor receptor.
Units
Counts
Participants
OG00025
OG0018
OG00212
Title
Denominators
Categories
Title
Measurements
OG0000
OG0012
OG0023
12
Title
Denominators
Categories
Title
Measurements
OG000NARP2D was not established as no DLTs were observed.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0033
Title
Denominators
Categories
Cycle 1 - day 1
Title
Measurements
Not done
OG0000
OG0010
OG0020
OG0030
Negative
OG0003
OG0013
OG0023
OG0033
Patient withdrawn
OG0000
OG0010
OG0020
OG0030
Cycle 3 - day 1
Title
Measurements
Not done
OG0000
OG0010
OG0020
OG003
End of treatment
Title
Measurements
Not done
OG0000
OG0010
OG0020
OG003
1-month follow-up
Title
Measurements
Not done
OG0000
OG0011
OG0020
OG003
Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. NSCLC = non-small cell lung cancer. METEx14Del = MET exon 14 skipping alteration. EGFR = epidermal growth factor receptor.
Units
Counts
Participants
OG00025
OG0018
OG00212
Title
Denominators
Categories
Cycle 1 - day 1
Title
Measurements
Not done
OG0000
OG0010
OG0020
Negative
OG00025
OG0018
OG00212
Positive
OG0000
OG0010
OG0020
Patient withdrawn
OG0000
OG0010
OG0020
Cycle 2 - day 1
Title
Measurements
Not done
OG0001
OG0010
OG0020
Negative
OG000
Cycle 3 - day 1
Title
Measurements
Not done
OG0001
OG0011
OG0020
Negative
OG000
Cycle 5 - day 1
Title
Measurements
Not done
OG0000
OG0010
OG0021
Negative
OG000
Cycle 7 - day 1
Title
Measurements
Not done
OG0000
OG0011
OG0020
Negative
OG000
End of treatment
Title
Measurements
Not done
OG0005
OG0010
OG0020
Negative
OG000
1-month follow up
Title
Measurements
Not done
OG0000
OG0011
OG0021
Negative
OG000
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0033
Title
Denominators
Categories
Title
Measurements
OG00017900(17100 to 24500)
OG00135700(31600 to 42900)
OG00282500(75200 to 86200)
OG00376800(55200 to 86400)
Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
Part 2 (Dose-Expansion): Patients in NSCLC METEx14Del Cohort
Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
Cohort of subjects receiving a dose of 24 mg/kg of Sym015 administered by intravenous infusion Q2W. Q2W = every second week.
Units
Counts
Participants
OG0003
OG0011
OG0021
OG0031
Title
Denominators
Categories
Title
Measurements
OG000179(116 to 179)
OG001137(137 to 137)
OG002193(193 to 193)
OG003170(170 to 170)
Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.
Part 2 (Dose-Expansion): Patients in NSCLC METEx14Del Cohort
Patients had advanced NSCLC with METEx14Del, and without available therapeutic options. Tumors did not need to be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Sym015 was administered at the recommended Phase 2 dose: 18 mg/kg loading dose followed by 12 mg/kg Q2W maintenance dose.