Open-label, Single-arm Trial to Evaluate Antitumor Activity, Safety, and Pharmacokinetics of Tusamitamab Ravtansine (SAR408701) Used in Combination With Ramucirumab or Ramucirumab and Pembrolizumab in Metastatic, Non-squamous, Non Small-cell Lung Cancer (NSQ NSCLC) Patients With CEACAM5-positive Tumors, Previously Treated With Platinum-based Chemotherapy and an Immune Checkpoint Inhibitor
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Sanofi
- Enrollment
- 31
- Locations
- 13
- Primary Endpoint
- Doublet Cohort - Part 1: Number of Participants With Study Drug-Related Dose-Limiting Toxicity (DLT)
Study Overview
Brief Summary
Primary Objectives:
Doublet Cohort
Part 1 (safety run-in):
To assess the tolerability and to confirm the recommended dose of tusamitamab ravtansine in combination with ramucirumab in the NSQ NSCLC population.
Part 2:
To assess the antitumor activity of tusamitamab ravtansine in combination with ramucirumab in the NSQ NSCLC population.
Triplet cohort
To assess the tolerability and to confirm the recommended dose of tusamitamab ravtansine in combination with ramucirumab and pembrolizumab in the NSQ NSCLC population.
Secondary Objectives:
Doublet Cohort
To assess the safety and tolerability of tusamitamab ravtansine in combination with ramucirumab.
To assess the durability of the response to treatment with tusamitamab ravtansine in combination with ramucirumab.
To assess anti-tumor activity of tusamitamab ravtansine in combination with ramucirumab on progression free survival (PFS) and disease control rate (DCR).
To assess the pharmacokinetic (PK) profiles of tusamitamab ravtansine (SAR408701) and ramucirumab when given in combination.
To assess the immunogenicity of tusamitamab ravtansine (SAR408701) when given in combination with ramucirumab.
Triplet cohort
To assess the safety and tolerability of tusamitamab ravtansine in combination with ramucirumab and pembrolizumab
To assess the antitumor activity of tusamitamab ravtansine in combination with ramucirumab and pembrolizumab in the NSQ NSCLC population.
To assess the immunogenicity of tusamitamab ravtansine when given in combination with ramucirumab and pembrolizumab
Detailed Description
The expected duration of the study intervention for participants may vary, based on progression date ; median expected duration of study per participant is estimated 11 months (up to 1 month for screening, a median of 6 months for treatment, and a median of 4 months for end-of-treatment assessments and safety follow-up visit)
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Ramucirumab + SAR408701
Ramucirumab will be administered intravenously prior to intravenously adminstration of SAR408701 every two 2 weeks.
Intervention: ramucirumab (Drug)
Ramucirumab + SAR408701
Ramucirumab will be administered intravenously prior to intravenously adminstration of SAR408701 every two 2 weeks.
Intervention: SAR408701 (Drug)
Ramucirumab + pembrolizumab +SAR408701
Participants will be treated with tusamitamab ravtansine and ramucirumab and pembrolizumab to assess the tolerability of the combination
Intervention: SAR408701 (Drug)
Ramucirumab + pembrolizumab +SAR408701
Participants will be treated with tusamitamab ravtansine and ramucirumab and pembrolizumab to assess the tolerability of the combination
Intervention: ramucirumab (Drug)
Ramucirumab + pembrolizumab +SAR408701
Participants will be treated with tusamitamab ravtansine and ramucirumab and pembrolizumab to assess the tolerability of the combination
Intervention: pembrolizumab (Drug)
Outcomes
Primary Outcomes
Doublet Cohort - Part 1: Number of Participants With Study Drug-Related Dose-Limiting Toxicity (DLT)
Time Frame: From Cycle 1 Day 1 up to Cycle 2 Day 14, approximately 28 days
The following AEs occurred during the first 2 cycles of treatment, unless due to disease progression or to a cause obviously unrelated to study drug, were considered DLTs: • Grade 4 neutropenia for 7 or more consecutive days. • Grade 3 to 4 neutropenia complicated by fever. • Grade \>=3 thrombocytopenia. • Elevated urine protein \>=3 gram(g)/24 hour. • Grade 4 non-hematologic AE. • Grade \>=3 keratopathy. • Grade 4 or refractory hypertension. In addition, any other AE that the Investigators and sponsor deemed to be dose limiting, regardless of its grade, was also considered as DLT.
Doublet Cohort - Part 2: Objective Response Rate (ORR)
Time Frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks
The ORR is defined as percentage of participants with confirmed complete response (CR) or partial response (PR) as best overall response (BOR) determined per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The CR is defined as disappearance of all target lesions. The PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Triplet Cohort: Number of Participants With Study Drug-Related Dose-Limiting Toxicity
Time Frame: From Cycle 1 Day 1 up to Cycle 1 Day 21
The following AEs occurred during the first cycle of treatment, unless due to disease progression or to a cause obviously unrelated to study drug, were considered DLTs: • Grade 4 neutropenia for 7 or more consecutive days. • Grade 3 to 4 neutropenia complicated by fever. • Grade \>=3 thrombocytopenia. • Elevated urine protein \>=3 g/24 hour. • Grade 4 non-hematologic AE. • Grade \>=3 keratopathy. • Grade 4 or refractory hypertension. In addition, any other AE that the Investigators and sponsor deemed dose limiting, regardless of its grade, was also considered as DLT.
Secondary Outcomes
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks)
- Number of Participants With Potentially Clinically Significant Abnormalities: Hematology(From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks)
- Number of Participants With Potentially Clinically Significant Abnormalities: Metabolism(From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks)
- Number of Participants With Potentially Clinically Significant Abnormalities: Electrolytes(From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks)
- Number of Participants With Potentially Clinically Significant Abnormalities: Renal Function(From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks)
- Number of Participants With Potentially Clinically Significant Abnormalities: Liver Function(From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks)
- Number of Participants With Potentially Clinically Significant Abnormalities: Electrocardiogram (ECG)(From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks)
- Number of Participants With Potentially Clinically Significant Abnormalities: Urinalysis(From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks)
- Doublet Cohort: Duration of Response (DOR)(Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks)
- Doublet Cohort: Progression-Free Survival (PFS)(Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks)
- Doublet Cohort: Disease Control Rate (DCR)(Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks)
- Triplet Cohort: Objective Response Rate(Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks)
- Doublet Cohort: Maximum Observed Concentration (Cmax) of Tusamitamab Ravtansine(Day 1 of Cycles 1 and 4)
- Doublet Cohort: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 14 Days (AUC0-14d) of Tusamitamab Ravtansine(Day 1 of Cycles 1 and 4)
- Doublet Cohort: Concentration Observed Before Treatment Administration During Repeated Dosing (Ctrough) of Ramucirumab(Cycle 2 Day 1)
- Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine(From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks)