Pleural mesothelioma Non-small cell lung cancer MedDRA version: 20.0 Level: PT Classification code 10035603 Term: Pleural mesothelioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Sanofi-Aventis Recherche & Développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Participant must be =18 years of age (or country’s legal age of majority if >18 years), at the time of signing the informed consent. - Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (cohorts A1, A2, B1, B2), Stage IV non-squamous NSCLC (cohort A3), or unresectable malignant pleural mesothelioma (cohort C1). - Cohort A1: PD-L1 expression TPS = 50%; Cohort A2: PD-L1 expression TPS 1 – 49% - Prior anticancer therapy: * Cohorts A1, A2, A3: No prior systemic therapy for advanced/metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development of metastatic disease. * Cohorts B1, B2: One prior anti-PD1/PD-L1 regimen (may include chemotherapy) plus one additional chemotherapy regimen * Cohort C1: One or two prior systemic treatments that include pemetrexed-based regimen in combination with platinum agent. - All cohorts must have a measurable disease - Mandatory baseline biopsy for the first 20 participants to enroll in cohorts A1, A2 - Cohorts B1 and B2: Based on the Investigator’s judgment, either docetaxel or pemetrexed is not the best treatment option for the participant. - Females are eligible to participate if they are not pregnant or breastfeeding, not a woman of childbearing potential (WOCBP) or are a WOCBP that agrees: * to use approved contraception method and submit to regular pregnancy testing prior to treatment and for 180 days after discontinuing study treatment * to refrain from donating or cryopreserving eggs for 180 days after discontinuing study treatment. - Males are eligible to participate if they agree to refrain from donating or cryopreserving sperm, and either abstain from heterosexual intercourse OR use approved contraception during study treatment and for at least 210 days after discontinuing study treatment. - 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 216 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 144
Exclusion criteria
Exclusion criteria: - Eastern Cooperative Oncology Group (ECOG) performance status of =2. - Poor bone marrow reserve - Poor organ function - Participants with baseline SpO2 =92%. - Active brain metastases or leptomeningeal disease. - History of allogenic or solid organ transplant - Last administration of prior antitumor therapy or any investigational treatment within 28 days or less than 5 times the half-life, whichever is shorter; major surgery or local intervention within 28 days. - Has received prior IL-2-based anticancer treatment. - Comorbidity requiring corticosteroid therapy - Antibiotic use (excluding topical antibiotics) =14 days prior to first dose of IMP - Severe or unstable cardiac condition within 6 months prior to starting study treatment - Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years - Known second malignancy either progressing or requiring active treatment within the last 3 years - Cohorts A1, A2, A3, C1: Prior treatment with an agent (approved or investigational) that blocks the PD1/PD-L1 pathway (participants who joined a study with an anti-PD1/PD-L1 but have written confirmation they were on control arm are allowed). - Receipt of a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the antitumor activity of SAR444245 in combination with other anticancer therapies;Secondary Objective: • To confirm the dose and to assess the safety profile of SAR444245 when combined with other anticancer therapies • To assess other indicators of antitumor activity • To assess the pharmacokinetic (PK) profile of SAR444245 when given in combination with pembrolizumab • To assess the immunogenicity of SAR444245;Primary end point(s): Objective response rate (ORR), defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR), derived based on Investigator’s assessment per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for Cohort A1, Cohort A2, Cohort A3, Cohort B1 and Cohort B2; per modified RECIST (mRECIST) for Cohort C1.;Timepoint(s) of evaluation of this end point: Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximatively 9 months after the last participant receive first dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) To confirm the dose and safety profile of SAR444245 when combined with other anticancer therapies: Incidence of Treatment Emergent Adverse Events (TEAEs), dose-limiting toxicities (DLT), SAEs, laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus gradings. 2) Time to response defined as the time from the first administration of IMP to the first documented evidence of PR (partial response) or CR (complete response) per RECIST 1.1 (for NSCLC) or mRECIST (for mesothelioma). 3) Duration of response (DoR), defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined per RECIST 1.1 (for NSCLC) or mRECIST (for mesothelioma) or death from any cause, whichever occurs first. 4) Clinical benefit rate (CBR) including CR or PR at any time plus stable disease (SD) of at least 6 months (per RECIST 1.1 [for NSCLC] or mRECIST [for mesothelioma]). 5) Progression free survival (PFS), defined as the time from the date of first IMP administration to the date of the first documented disease progression as per RECIST 1.1 for NSCLC) or mRECIST (for mesothelioma) or death due to any cause, whichever occurs first. 6) To assess the plasma concentrations of SAR444245 7) To assess the incidence of anti-drug antibodies (ADAs) against SAR444245.;Timepoint(s) of evaluation of this end point: 1) DLTs: The DLT observation period is 1 cycle (21 days); SAE: from 1st IMP dose up to 90 days after the last dose of IMP; AE/TEAE: from 1st IMP dose up to 30 days after the last dose of IMP 2,3,4,5) Baseline to the date of first documentation of progression, or initiation of subsequent anticancer therapy 6) At Day1, Day2, Day3 of Cycle1 and Day 1 of Cycle 2-4-7-10 + every 5th cycle. Cycle is 21 days. 7) At Day1 and Day 15 of Cycle1, at Day 1 of Cycle 2-4-7-10 + every 5th cycle and 30 days | — |
Countries
Australia, France, Italy, Japan, Korea, Democratic People's Republic of, Poland, Spain, Taiwan, United States
Contacts
Public ContactUnidad de Estudios Clínicos
Sanofi-Aventis, S.A
Outcome results
None listed