o Part 1 (safety run-in): To assess the tolerability and to confirm the recommended dose of
SAR408701 in combination with ramucirumab in the NSQ NSCLC population.
o Part 2: To assess the antitumor activity of SAR408701 in combination with ramucirumab in
the NSQ NSCLC population.
- To assess the safety and tolerability of SAR408701 in combination with ramucirumab
- To assess the durability of the response to treatment with SAR408701 in combination with
- To assess efficacy of SAR408701 in combination with ramucirumab on progression free
- To assess the pharmacokinetic (PK) profile of SAR408701 and ramucirumab when given in
- To assess the immunogenicity of SAR408701 when given in combination with ramucirumab
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)
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.
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
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
- Radiographic evidence of major airway or blood vessel invasion or intratumor
- History of uncontrolled hereditary or acquired thrombotic disorder or history of
- 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
- 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
- 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
- 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
- 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
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.