Pleural mesothelioma, Non-small cell lung cancer
Conditions
Interventions
Drug: SAR444245 (THOR-707)
Pharmaceutical Form: Solution for infusion, Route of Administration: intravenous infusion
Drug: Pembrolizumab
Pharmaceutical Form: Solution for infusion, Route of Administ
Sponsors
Obara Kentaro
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 and B1) 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 and A2: 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. - Cohort B1: 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 - Cohort B1: 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 150 days after discontinuing study treatment - - to refrain from donating or cryopreserving eggs for 150 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.
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: - 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 tissue/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 and 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 |
|---|---|
| 1. Objective response rate (ORR) [ Time Frame: 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. ] 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 and Cohort B1; per modified RECIST (mRECIST) for Cohort C1. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.To confirm the dose [ Time Frame: Observation period is 1 cycle (21 days) ] Incidence of Dose-limiting toxicities (DLTs) during DLT observation period 2. Assessment of SAR444245 safety profile when combined with other anticancer therapies-Treatment Emergent Adverse Events [ Time Frame: From 1st IMP dose up to 30 days after the last dose of IMP ] Incidence of Treatment Emergent Adverse Events (TEAEs) and 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 3. Assessment of SAR444245 safety profile when combined with other anticancer therapies-Serious Adverse Events [ Time Frame: From 1st IMP dose up to 90 days after the last dose of IMP ] Incidence of Serious Adverse Events (SAEs) and 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 4. Time to response [ Time Frame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months ] Time to response (TTR) defined as the time from the first administration of investigational medicinal product (IMP) to the first tumor assessment at which the overall response was recorded as PR or CR that is subsequently confirmed and determined by investigator per RECIST 1.1 (for NSCLC) or mRECIST (for mesothelioma). 5. Duration of response [ Time Frame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months ] Duration of response (DoR), defined as the time from first tumor assessment at which the overall response was recorded as PR or CR that is subsequently confirmed until progressive disease (PD) determined by inves | — |
Countries
Argentina, Australia, Chile, France, Italy, Japan, Poland, Republic of Korea, Spain, Taiwan, United States
Contacts
Public ContactUnit Clinical
Sanofi K.K.
Outcome results
None listed