SAR408701 in Combination With Ramucirumab in Pre-treated Patients With Non Squamous Non-small Cell Lung Cancer (NSQ NSCLC) (CARMEN-LC04)

Brief description of study

Primary Objectives:

  • 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.
  • Part 2: To assess the antitumor activity of SAR408701 in combination with ramucirumab in the NSQ NSCLC population.

Secondary Objectives:

  • 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 ramucirumab
  • To assess efficacy of SAR408701 in combination with ramucirumab on progression free survival
  • To assess the pharmacokinetic (PK) profile of SAR408701 and ramucirumab when given in combination
  • To assess the immunogenicity of SAR408701 when given in combination with ramucirumab

Detailed description of study

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)

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Non-small Cell Lung Cancer Metastatic
  • Age: 18 Years
  • Gender: Male or Female

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 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
        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.

Updated on 21 Nov 2022 . Study ID: NCT04394624

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