Non-squamous non–small-cell lung cancer (NSQ NSCLC) MedDRA version: 20.0 Level: LLT Classification code 10079440 Term: Non-squamous non-small cell lung cancer System Organ Class: 100000004864
Conditions
Interventions
Product Code: SAR408701
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not assigned
Current Sponsor code: SAR408701
Other descriptive name: SAR408701
Concentration uni
Sponsors
Sanofi aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSQ NSCLC with no EGFR sensitizing mutation or BRAF mutation or ALK/ROS alterations. - No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease). - Expression of CEACAM5 as demonstrated prospectively by a centrally assessed IHC assay of =2+ in intensity involving at least 50% of the tumor cell population in archival tumor sample (or if not available fresh biopsy sample). - PD-L1 positive tumor (TPS =1%) as determined locally by an approved test - Measurable disease based on RECIST 1.1. - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies - Capable of giving signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: - Medical condition reauiring concomitant administration of a medication with a narrow therapeutic window and metabolized by CYP450 or astrong CTP3A inhibitor. - Untreated brain metastases and history of leptomeningeal disease. - Significant concomitant illness, including any severe medical condition that, in the opinion of the investigator or Sponsor, 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. - History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or active hepatitis A, B, or C infection. - 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 randomization or active tuberculosis. - Interstitial lung disease or history of pneumonitis that has required oral or IV steroids - Non-resolution of any prior treatment-related toxicity to = Grade 2 according to NCI CTCAE V5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone replacement therapy. - Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy. The use of contact lenses is not permitted. - Symptomatic herpes zoster within 3 months prior to screening. - Significant allergies to humanized monoclonal antibodies. - Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis). - Concurrent treatment with any other anticancer therapy. - Have received prior chemotherapy treatment for advanced/metastatic NSCLC. - The patient is a candidate for a curative treatment with either surgical resection and/or chemoradiation - Washout period before the first administration of study intervention of less than 3 weeks or less than 5 times the half-life, whichever is longer, for any investigational treatment). - Any prior therapy targeting CEACAM5. - Any prior treatment with any other anti-PD-1, or PD-L1 or programmed death ligand 2 (PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4. - Any prior maytansinoid treatment (DM1 or DM4 ADC). - Is receiving systemic steroid therapy =3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication. Daily steroid replacement therapy or any corticosteroid premedication if applicable are allowed. - 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. - Any major surgery within the preceding 3 weeks of the first study intervention administration. Prior/concurrent clinical study experience - Current participation in any other clinical study involving an investigational study treatment or any other type of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Part 1 (safety run-in): To assess the tolerability and to confirm the recommended dose of SAR408701 in combination with pembrolizumab in the NSQ NSCLC population •Part 2: To assess the antitumor activity of SAR408701 in combination with pembrolizumab and pembrolizumab single agent in the NSQ NSCLC population ;Secondary Objective: •To assess the safety and tolerability of SAR408701 in combination with pembrolizumab and pembrolizumab single agent •To assess the durability of the response to treatment with SAR408701 in combination with pembrolizumab and pembrolizumab single agent •To assess the efficacy on progression-free survival (PFS) of SAR408701 in combination with pembrolizumab and pembrolizumab single agent •To assess the pharmacokinetics (PK) of SAR408701 and pembrolizumab when given in combination, and of pembrolizumab when given as a single agent •To assess the immunogenicity of SAR408701 when given in combination with pembrolizumab ;Primary end point(s): Part 1: Number of partcipants with study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21) - Study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21), including but not limited to corneal toxicity Part 2: Objective response rate (ORR) of SAR408701 + pembrolizumab and pembrolizumab single agent - ORR is defined as proportion of participants who have a confirmed complete response (CR) or partial response (PR) as per response evaluation criteria in solid tumors (RECIST v1.1);Timepoint(s) of evaluation of this end point: Part 1 and Part 2 : Baseline up to 10 months after last participant treated | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities - TEAEs, SAEs and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5 2. Duration of response - Duration of response (DOR), defined as the time from first documented evidence of CR or PR until progressive disease determined per RECIST 1.1 or death from any cause, whichever occurs first 3. Progression-free surviva - Progression-free survival, defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever comes first 4. Ceoi of SAR408701 and pembrolizumab - Concentration observed at the end of IV infusion (Ceoi) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone 5. Cmax of SAR408701 and pembrolizumab - Maximum concentration observed after infusion (Cmax) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone 6. Tmax of SAR408701 and pembrolizumab - Time to reach Cmax (Tmax) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone 7. Clast of SAR408701 and pembrolizumab - Last concentration observed above the lower limit of quantification after infusion (Clast)of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone 8. Tlast of SAR408701 and pembrolizumab - Time of Clast (Tlast) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone;Timepoint(s) of evaluation of this end point: 1. to 8. : Baseline up to 10 months after last participant treated | — |
Countries
Czech Republic, France, Hungary, Israel, Spain, United States
Contacts
Public ContactDirection des Opérations Cliniques
Sanofi-aventis France
Outcome results
None listed