Non-small Cell Lung Cancer MetastaticPhase 2CARMEN-LC04NCT04394624
Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab or Ramucirumab and Pembrolizumab in Pretreated Patients With NSQ NSCLC (CARMEN-LC04)
A Phase 2 study testing SAR408701, ramucirumab and pembrolizumab in people with Non-small Cell Lung Cancer Metastatic, run by Sanofi at 13 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Metastatic
- What is being tested?
- SAR408701, ramucirumab and pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 13 sitesin 6 countries
- Study dates
- 31 Aug 2020to 24 Oct 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Metastatic disease progression fulfilling both of the following 2 criteria:
- 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
- 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.
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 40Show fewer
- 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 exclusion criteria for potential participants
- Triplet cohort exclusions
- History of active autoimmune disease that has required systemic treatment in the past 2 years.
- History of allogeneic tissue/solid organ transplantation.
- Active infection requiring IV systemic therapy within 2 weeks prior to first study intervention administration or active tuberculosis.
- Interstitial lung disease or history of pneumonitis that has required oral or IV steroids.
- Symptomatic herpes zoster within 3 months prior to screening.
- Significant allergies to humanized monoclonal antibodies.
- Any radiation therapy to lung >30 Gy within 6 months of first study intervention administration.
- Has received or will receive a live vaccine within 30 days prior to the first study intervention administration.
- Thyroid-stimulating hormone (TSH) out of normal limits. If TSH is not within normal limits at baseline, the subject may still be eligible if T3 and free T4 are within the normal limits
- The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Trial locations and contacts
13 sites in 6 countries.
13 sites in 6 countries
Spain4 sites
Investigational Site Number : 7240001
Barcelona / Sabadell, Catalunya [Cataluña], 08208
Investigational Site Number : 7240005
Madrid, Madrid, Comunidad de, 28046
Investigational Site Number : 7240004
Madrid, 28040
Investigational Site Number : 7240003
Zaragoza, 50009
United States3 sites
Roswell Park Cancer Institute Site Number : 8400003
Buffalo, New York, 14263
Henry Ford Hospital Site Number : 8400005
Detroit, Michigan, 48202
McClinton Cancer Center Site Number : 8400002
Waco, Texas, 76712
Czechia2 sites
Investigational Site Number : 2030001
Ostrava - Vitkovice, 703 84
Investigational Site Number : 2030002
Prague, 12808
South Korea2 sites
Investigational Site Number : 4100001
Seoul, Seoul-teukbyeolsi, 03080
Investigational Site Number : 4100002
Seoul, Seoul-teukbyeolsi, 03722
About this study
Official title: 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
Primary Objectives:
Doublet Cohort
Read more
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
Read the 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)
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Being tested
- SAR408701, ramucirumab, pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAR408701Drug
Pharmaceutical form:concentrate for solution for injection Route of administration: intravenous infusion
ramucirumabDrug
Pharmaceutical form: concentrate for solution for injection Route of administration: intravenous infusion
pembrolizumabDrug
Pharmaceutical form: concentrate for solution for injection Route of administration: intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Ramucirumab + SAR408701 | Experimental | Ramucirumab will be administered intravenously prior to intravenously adminstration of SAR408701 every two 2 weeks. Receives: Drug: SAR408701; Drug: ramucirumab |
| Ramucirumab + pembrolizumab +SAR408701 | Experimental | Participants will be treated with tusamitamab ravtansine and ramucirumab and pembrolizumab to assess the tolerability of the combination Receives: Drug: SAR408701; Drug: ramucirumab; Drug: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Cycle 1 Day 1 up to Cycle 2 Day 14, approximately 28 days
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.
Measured: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks
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.
Measured: From Cycle 1 Day 1 up to Cycle 1 Day 21
Secondary outcomes (16)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Measured: 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
Blood samples were collected to determine the hematology laboratory clinically significant abnormalities.
Measured: 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
Blood samples were collected to determine the clinically significant abnormalities in metabolism.
Measured: 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
Blood samples were collected to determine the clinically significant abnormalities in electrolytes.
Measured: 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
Blood samples were collected to determine the renal function laboratory clinically significant abnormalities.
Measured: 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
Blood samples were collected to determine the liver function laboratory clinically significant abnormalities.
Measured: 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)
A single 12-lead ECG was recorded using an ECG machine that automatically calculates the heart rate and measures PR, QRS, and QT intervals.
Measured: 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
Urine samples were collected to determine the clinically significant abnormalities in urine.
Measured: 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)
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.
Measured: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks
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.
Measured: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks
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.
Measured: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks
Triplet Cohort: Objective Response Rate
The ORR is defined as percentage of participants with confirmed CR or PR as BOR determined per RECIST v1.1.
Measured: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks
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.
Measured: 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
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.
Measured: Day 1 of Cycles 1 and 4
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.
Measured: Cycle 2 Day 1
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.
Measured: From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2020
- Study start31 Aug 2020
- Primary completion6 Mar 2023
- Study completion24 Oct 2024
Why it stopped: Sponsor decision, the decision is not related to any safety concern.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-small Cell Lung Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04394624
- Sponsor's protocol ID
- ACT16525
- Other IDs
- U1111-1244-1585, 2019-003914-15, 2019
- Acronym
- CARMEN-LC04
- Status last verified
- May 2025
- First submitted
- 14 May 2020
- Last updated
- 6 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04394624
- Acronym / sponsor ID
- CARMEN-LC04 / ACT16525
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision, the decision is not related to any safety concern.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2020 (actual)
- Primary completion
- 6 Mar 2023 (actual)
- Study completion
- 24 Oct 2024 (actual)
- First posted
- 19 May 2020 (actual)
- Results
- Posted 28 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ramucirumab + SAR408701 | Experimental | Drug: SAR408701, Drug: ramucirumabRamucirumab will be administered intravenously prior to intravenously adminstration of SAR408701 every two 2 weeks. |
| Ramucirumab + pembrolizumab +SAR408701 | Experimental | Drug: SAR408701, Drug: ramucirumab, Drug: pembrolizumabParticipants will be treated with tusamitamab ravtansine and ramucirumab and pembrolizumab to assess the tolerability of the combination |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Metastatic disease progression fulfilling both of the following 2 criteria:
- AND
- 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.
Key exclusion criteria (40 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAR408701Pharmaceutical form:concentrate for solution for injection Route of administration: intravenous infusion | Drug | Ramucirumab + SAR408701, Ramucirumab + pembrolizumab +SAR408701 |
| ramucirumabPharmaceutical form: concentrate for solution for injection Route of administration: intravenous infusion | Drug | Ramucirumab + SAR408701, Ramucirumab + pembrolizumab +SAR408701 |
| pembrolizumabPharmaceutical form: concentrate for solution for injection Route of administration: intravenous infusion | Drug | Ramucirumab + pembrolizumab +SAR408701 |
Primary outcome
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.
16 secondary outcomes
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks
Doublet Cohort: Progression-Free Survival (PFS)
Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks
Doublet Cohort: Disease Control Rate (DCR)
Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks
Triplet Cohort: Objective Response Rate
Time frame: Tumor assessments performed at baseline, and every 8 weeks +/-7 days thereafter, approximately 130 weeks
Doublet Cohort: Maximum Observed Concentration (Cmax) of Tusamitamab Ravtansine
Time frame: 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
Time frame: Day 1 of Cycles 1 and 4
Doublet Cohort: Concentration Observed Before Treatment Administration During Repeated Dosing (Ctrough) of Ramucirumab
Time frame: Cycle 2 Day 1
Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine
Time frame: From first dose of study drug (Day 1) up to Day 30 post last dose of study drug, approximately 134 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Related trials for Non-small Cell Lung Cancer Metastatic
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 3
Study of Daraxonrasib (RMC-6236) in Patients With RAS Mutated NSCLC (RASolve 301)
NSCLC (Non-small Cell Lung Cancer), Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
13 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SAR408701, ramucirumab and pembrolizumab in people with Non-small Cell Lung Cancer Metastatic, run by Sanofi at 13 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Spain, United States, Czechia, South Korea, Bulgaria and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2025.