Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab or Ramucirumab and Pembrolizumab in Pretreated Patients With NSQ NSCLC (CARMEN-LC04)
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Interventions
- Registration Number
- NCT04394624
- Lead Sponsor
- Sanofi
- 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)
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 31
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ramucirumab + pembrolizumab +SAR408701 SAR408701 Participants will be treated with tusamitamab ravtansine and ramucirumab and pembrolizumab to assess the tolerability of the combination Ramucirumab + SAR408701 SAR408701 Ramucirumab will be administered intravenously prior to intravenously adminstration of SAR408701 every two 2 weeks. Ramucirumab + SAR408701 ramucirumab Ramucirumab will be administered intravenously prior to intravenously adminstration of SAR408701 every two 2 weeks. Ramucirumab + pembrolizumab +SAR408701 pembrolizumab Participants will be treated with tusamitamab ravtansine and ramucirumab and pembrolizumab to assess the tolerability of the combination Ramucirumab + pembrolizumab +SAR408701 ramucirumab Participants will be treated with tusamitamab ravtansine and ramucirumab and pembrolizumab to assess the tolerability of the combination
- Primary Outcome Measures
Name Time Method Doublet Cohort - Part 1: Number of Participants With Study Drug-Related Dose-Limiting Toxicity (DLT) 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) Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 106 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 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 Outcome Measures
Name Time Method Doublet Cohort: Duration of Response (DOR) Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 106 weeks The DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined per RECIST v1.1 or death from any cause, whichever occurs first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Doublet Cohort: Progression-Free Survival (PFS) Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 106 weeks The PFS is defined as the time from the first study drug administration to the date of the first documented disease progression or death due to any cause, whichever comes first.
Doublet Cohort: Disease Control Rate (DCR) Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 106 week The DCR is defined as the percentage of participants who achieved confirmed CR, confirmed PR or stable disease (SD) as per RECIST v1.1. The SD is defined as neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Doublet Cohort: Maximum Observed Concentration (Cmax) of Tusamitamab Ravtansine and Ramucirumab Tusamitamab ravtansine: At start of every infusion for each cycle up to Cycle 13; Ramucirumab: At start of infusion at Cycle 7 Blood samples were collected for the measurement of Cmax of tusamitamab ravtansine and ramucirumab concentrations. Cmax of tusamitamab ravtansine will be calculated using non-compartmental method.
Doublet and Triplet Cohorts: Number of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 110 weeks A single 12-lead ECG was recorded using an ECG machine that automatically calculates the heart rate and measures PR, QRS, and QT intervals.
Doublet and Triplet Cohorts: 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 110 weeks An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A SAE is defined as any untoward medical occurrence that, at any dose: results in death or life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent disability/incapacity or congenital anomaly/birth defect. TEAE is defined as AEs that develop, worsen, or become serious during the treatment period.
Doublet Cohort: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 14 Days (AUC0-14d) of Tusamitamab Ravtansine and Ramucirumab Tusamitamab ravtansine: At start of every infusion for each cycle up to Cycle 13; Ramucirumab: At start of infusion at Cycle 7 Blood samples were collected for the measurement of AUC0-14d of tusamitamab ravtansine and ramucirumab concentrations. AUC0-14d will be calculated using the trapezoidal method from time 0 to 14 days and non-compartmental method.
Doublet and Triplet Cohorts: 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 110 weeks Blood samples were collected to assess the presence of ATA against tusamitamab ravtansine in plasma from all participants.
Doublet and Triplet Cohorts: Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Laboratory Parameters From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 110 weeks Blood samples were collected to determine the clinical chemistry laboratory abnormalities.
Doublet and Triplet Cohorts: Number of Participants With Potentially Clinically Significant Abnormalities in Urinalysis From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 110 weeks Urine samples were collected to determine the clinical chemistry laboratory abnormalities.
Doublet Cohort: Concentration Observed Before Treatment Administration During Repeated Dosing (Ctrough) of Tusamitamab Ravtansine and Ramucirumab Tusamitamab ravtansine: At start of every infusion for each cycle up to Cycle 13; Ramucirumab: At start of infusion at Cycle 7 Blood samples were collected for the measurement of Ctrough of tusamitamab ravtansine and ramucirumab concentrations. Ctrough of tusamitamab ravtansine was calculated using non-compartmental method.
Triplet Cohort: Objective Response Rate Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 106 weeks The ORR is defined as percentage of participants with confirmed CR or PR as BOR determined per RECIST v1.1.
Trial Locations
- Locations (13)
Investigational Site Number : 6200001
🇵🇹Porto, Portugal
Henry Ford Hospital Site Number : 8400005
🇺🇸Detroit, Michigan, United States
Roswell Park Cancer Institute Site Number : 8400003
🇺🇸Buffalo, New York, United States
McClinton Cancer Center Site Number : 8400002
🇺🇸Waco, Texas, United States
Investigational Site Number : 4100001
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 2030002
🇨🇿Praha 2, Czechia
Investigational Site Number : 1000001
🇧🇬Plovdiv, Bulgaria
Investigational Site Number : 2030001
🇨🇿Ostrava - Vitkovice, Czechia
Investigational Site Number : 4100002
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 7240001
🇪🇸Barcelona / Sabadell, Catalunya [Cataluña], Spain
Investigational Site Number : 7240005
🇪🇸Madrid, Madrid, Comunidad De, Spain
Investigational Site Number : 7240004
🇪🇸Madrid, Spain
Investigational Site Number : 7240003
🇪🇸Zaragoza, Spain