Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab or Ramucirumab and Pembrolizumab in Pretreated Patients With NSQ NSCLC (CARMEN-LC04)

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04394624

Acronym

CARMEN-LC04

Enrollment

Registered

2020-05-19

Start date

2020-08-31

Completion date

2024-10-24

Last updated

2025-06-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-small Cell Lung Cancer Metastatic

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)

Interventions

DRUGSAR408701

Pharmaceutical form:concentrate for solution for injection Route of administration: intravenous infusion

DRUGramucirumab

Pharmaceutical form: concentrate for solution for injection Route of administration: intravenous infusion

DRUGpembrolizumab

Pharmaceutical form: concentrate for solution for injection Route of administration: intravenous infusion

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

: * Metastatic disease progression fulfilling both of the following 2 criteria: 1. Having progressive disease during or after platinum-based chemotherapy (at least 2 cycles). Maintenance therapy following platinum-based chemotherapy is not considered as a separate regimen. Adjuvant/neoadjuvant treatment for a patient who had a relapse with metastatic disease during or within 6 months of completing treatment will be considered as first-line treatment. AND 2. Having progressive disease during or after 1 immune checkpoint inhibitor (anti-PD1/PD-L1); this could be given as monotherapy or in combination with platinum-based chemotherapy (whatever the order). * Participants with carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5 expression of ≥2+ in archival tumor sample (or if not available, fresh biopsy sample) involving at least 50 % of the tumor cell population as demonstrated prospectively by central laboratory via immune histochemistry (IHC). * At least one measurable lesion by RECIST v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * A female participant who agrees to use effective contraceptive methods during and for at least 7 months after the last dose of study intervention. * A male participant who agrees to use effective contraception methods during and for at least 4 months after the last dose of study intervention * Signed informed consent

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply: * Patients with untreated brain metastases and history of leptomeningeal disease. * Significant concomitant illnesses that would impair the patient's participation in the study or interpretation of the results. * History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment. * Non-resolution of any prior treatment related toxicity to \< grade 2 according to NCI CTCAE V5.0, except for alopecia, vitiligo and active thyroiditis controlled with hormonal replacement therapy * History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or unresolved viral hepatitis * Previous history of and/or unresolved corneal disorders. The use of contact lenses is not permitted. * Radiographic evidence of major airway or blood vessel invasion or intratumor cavitation * History of uncontrolled hereditary or acquired arterial thrombotic disorder or history of aneurism. * Major surgery within 28 days prior to Day 1/first IMP infusion,. Postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months. * History of gross hemoptysis within 2 months before the first administration of study intervention. * Clinically relevant congestive heart failure (CHF; NYHA II-IV, or LVEF less than 50%) or symptomatic or poorly controlled cardiac arrhythmia. * Any arterial thrombotic event within 6 months before the first administration of study intervention. * Uncontrolled arterial hypertension (systolic ≥150 mmHg or diastolic ≥90 mmHg) despite standard medical management. * Serious or nonhealing wound, skin ulcer, or bone fracture within 28 days before the first administration of study intervention. * Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to first administration of study intervention. * Significant bleeding disorders, vasculitis, or Grade 3-4 gastrointestinal (GI) bleeding within 3 months before the first administration of study intervention. * Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection Crohn's disease, ulcerative colitis, or chronic diarrhea. * Medical condition requiring concomitant administration of a medication with a narrow therapeutic window and metabolized by CYP450 or a strong CYP3A inhibitor * Concurrent treatment with any other anticancer therapy * No more than 1-line previous chemotherapy in metastatic setting * Prior treatment with ramucirumab or docetaxel * Prior therapy targeting CEACAM5 or maytansinoid treatment (DM1 or DM4 antibody-drug conjugate) * Contraindication to use of corticosteroid premedication * Current therapeutic anticoagulation with warfarin, low-molecular-weight heparin, or similar agents. Patients receiving prophylactic, low-dose anticoagulation therapy are eligible * Previous enrollment in this study, current participation in any other clinical study involving an investigational study treatment, or any other type of medical research * Poor bone marrow, liver or kidney functions * Urine dipstick or routine analysis indicating proteinuria of 2+ or higher, unless a 24 hour urine collection demonstrates \<1000 mg of protein. * Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.Most important

Design outcomes

Primary

Measure	Time frame	Description
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 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	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

Measure	Time frame	Description
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	Blood samples were collected to determine the clinically significant abnormalities in electrolytes.
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	Blood samples were collected to determine the renal function laboratory clinically significant abnormalities.
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	Blood samples were collected to determine the liver function laboratory clinically significant abnormalities.
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	A single 12-lead ECG was recorded using an ECG machine that automatically calculates the heart rate and measures PR, QRS, and QT intervals.
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	Urine samples were collected to determine the clinically significant abnormalities in urine.
Doublet Cohort: Duration of Response (DOR)	Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 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.
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	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: Disease Control Rate (DCR)	Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks	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.
Triplet Cohort: Objective Response Rate	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 CR or PR as BOR determined per RECIST v1.1.
Doublet Cohort: Maximum Observed Concentration (Cmax) of Tusamitamab Ravtansine	Day 1 of Cycles 1 and 4	Blood samples were collected for the measurement of Cmax of tusamitamab ravtansine concentrations. Cmax of tusamitamab ravtansine was calculated using non-compartmental method.
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	Blood samples were collected for the measurement of AUC0-14d of tusamitamab ravtansine concentrations. AUC0-14d was calculated using the trapezoidal method from time 0 to 14 days and non-compartmental method.
Doublet Cohort: Concentration Observed Before Treatment Administration During Repeated Dosing (Ctrough) of Ramucirumab	Cycle 2 Day 1	Blood samples were collected for the measurement of Ctrough of ramucirumab concentrations. Ctrough was calculated using non-compartmental method.
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	Blood samples were collected to assess the presence of ATA against tusamitamab ravtansine in plasma from all participants. Treatment-emergent ATA is defined as participant with at least 1 treatment-induced/boosted ATA during the treatment period.
Doublet Cohort: Progression-Free Survival (PFS)	Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 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.
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	Blood samples were collected to determine the hematology laboratory clinically significant abnormalities.
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	Blood samples were collected to determine the clinically significant abnormalities in metabolism.

Countries

Bulgaria, Czechia, Portugal, South Korea, Spain, United States

Participant flow

Recruitment details

The study was conducted at 10 centers in 5 countries. A total of 37 participants were screened between 31 August 2020 and 03 October 2022, of which 6 were screen failures. Screen failures were mainly due to not meeting the criteria for inclusion. The study was prematurely terminated due to the discontinuation of the overall development of tusamitamab ravtansine (SAR408701) by the sponsor.

Pre-assignment details

A total of 31 participants were enrolled in the study. No participants were enrolled in the triplet cohort due to the early termination of the study.

Participants by arm

Arm	Count
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab Participants received tusamitamab ravtansine 100 mg/m\^2 and ramucirumab 8 mg/kg IV infusion Q2W until disease progression, unacceptable AE, or the participant's or investigator's decision to stop the treatment.	31
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab + Pembrolizumab Participants were planned to receive tusamitamab ravtansine 150 mg/m\^2 plus ramucirumab 10 mg/kg and pembrolizumab 200 mg IV infusion Q3W until disease progression, unacceptable AE, or the participant's or investigator's decision to stop the treatment.	0
Total	31

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	6
Overall Study	Not related to COVID-19	1
Overall Study	Progressive disease	24

Baseline characteristics

Characteristic	Total	Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab
Age, Continuous	62.7 years STANDARD_DEVIATION 10.1	62.7 years STANDARD_DEVIATION 10.1
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants
Race (NIH/OMB) Asian	13 Participants	13 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants
Race (NIH/OMB) White	18 Participants	18 Participants
Sex: Female, Male Female	16 Participants	16 Participants
Sex: Female, Male Male	15 Participants	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	13 / 31	0 / 0
other Total, other adverse events	31 / 31	0 / 0
serious Total, serious adverse events	7 / 31	0 / 0

Outcome results

Primary

Doublet Cohort - Part 1: Number of Participants With Study Drug-Related Dose-Limiting Toxicity (DLT)

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.

Time frame: From Cycle 1 Day 1 up to Cycle 2 Day 14, approximately 28 days

Population: DLT-evaluable (Part 1) population included all enrolled participants who received 2 cycles with at least 80% of the intended dose for both tusamitamab ravtansine and ramucirumab at each of the 2 first infusions unless they discontinued the study intervention before the end of Cycle 2 due to a DLT.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab	Doublet Cohort - Part 1: Number of Participants With Study Drug-Related Dose-Limiting Toxicity (DLT)	0 Participants

Primary

Doublet Cohort - Part 2: Objective Response Rate (ORR)

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.

Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks

Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.

Arm	Measure	Value (NUMBER)
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab	Doublet Cohort - Part 2: Objective Response Rate (ORR)	22.6 percentage of participants

Primary

Triplet Cohort: Number of Participants With Study Drug-Related Dose-Limiting Toxicity

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.

Time frame: From Cycle 1 Day 1 up to Cycle 1 Day 21

Population: No participants were enrolled in the triplet cohort due to the early termination of the study.

Secondary

Doublet Cohort: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 14 Days (AUC0-14d) of Tusamitamab Ravtansine

Blood samples were collected for the measurement of AUC0-14d of tusamitamab ravtansine concentrations. AUC0-14d was calculated using the trapezoidal method from time 0 to 14 days and non-compartmental method.

Time frame: Day 1 of Cycles 1 and 4

Population: The PK population included all participants from the all-treated population with at least 1 post-baseline PK concentration with adequate documentation of dosing and sampling dates and times. Only participants analyzed and data collected at specific timepoints are reported.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab	Doublet Cohort: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 14 Days (AUC0-14d) of Tusamitamab Ravtansine	Cycle 1 Day 1	312 day*mcg/mL	Standard Deviation 71.3
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab	Doublet Cohort: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 14 Days (AUC0-14d) of Tusamitamab Ravtansine	Cycle 4 Day 1	459 day*mcg/mL	Standard Deviation 26.8

Secondary

Doublet Cohort: Concentration Observed Before Treatment Administration During Repeated Dosing (Ctrough) of Ramucirumab

Blood samples were collected for the measurement of Ctrough of ramucirumab concentrations. Ctrough was calculated using non-compartmental method.

Time frame: Cycle 2 Day 1

Arm	Measure	Value (MEAN)	Dispersion
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab	Doublet Cohort: Concentration Observed Before Treatment Administration During Repeated Dosing (Ctrough) of Ramucirumab	32481.7 nanogram/mL	Standard Deviation 11656.52

Secondary

Doublet Cohort: Disease Control Rate (DCR)

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.

Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks

Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.

Arm	Measure	Value (NUMBER)
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab	Doublet Cohort: Disease Control Rate (DCR)	83.9 percentage of participants

Secondary

Doublet Cohort: Duration of Response (DOR)

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.

Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks

Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered. Only responders (participants with CR or PR with confirmation of response by investigator) were analyzed in this outcome measure.

Arm	Measure	Value (MEDIAN)
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab	Doublet Cohort: Duration of Response (DOR)	11.07 months

Secondary

Doublet Cohort: Maximum Observed Concentration (Cmax) of Tusamitamab Ravtansine

Blood samples were collected for the measurement of Cmax of tusamitamab ravtansine concentrations. Cmax of tusamitamab ravtansine was calculated using non-compartmental method.

Time frame: Day 1 of Cycles 1 and 4

Population: The Pharmacokinetic (PK) population included all participants from the all-treated population with at least 1 post-baseline PK concentration with adequate documentation of dosing and sampling dates and times. Only participants analyzed and data collected at specific timepoints are reported.

Arm	Measure	Group	Value (MEAN)	Dispersion
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab	Doublet Cohort: Maximum Observed Concentration (Cmax) of Tusamitamab Ravtansine	Cycle 1 Day 1	70.0 microgram per milliliter (mcg/mL)	Standard Deviation 11.9
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab	Doublet Cohort: Maximum Observed Concentration (Cmax) of Tusamitamab Ravtansine	Cycle 4 Day 1	82.5 microgram per milliliter (mcg/mL)	Standard Deviation 16.3

Secondary

Doublet Cohort: Progression-Free Survival (PFS)

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.

Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks

Population: All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.

Arm	Measure	Value (MEDIAN)
Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab	Doublet Cohort: Progression-Free Survival (PFS)	5.95 months

Secondary

Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine

Blood samples were collected to assess the presence of ATA against tusamitamab ravtansine in plasma from all participants. Treatment-emergent ATA is defined as participant with at least 1 treatment-induced/boosted ATA during the treatment period.