Solid tumor
Conditions
Interventions
Drug: SAR445877, Pharmaceutical form: Concentrate for solution for infusion
Drug: Cetuximab (Erbitux), Pharmaceutical form: Solution for infusion
Drug: ADG126, Pharmaceutical form: Solution for inf
Sponsors
Obara Kentaro
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Dose escalation Part 1A and Japan Cohort F: - Participants with advanced unresectable or metastatic solid tumors for which, in the judgement of the investigator, no standard alternative therapy is available or is not in the best interest of the participant. 2. Dose escalation Part 1B: Participants with advanced unresectable or metastatic melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), colorectal cancer (CRC) (microsatellite instability-high [MSI-H]/deficient mismatch repair [dMMR]), malignant pleural mesothelioma or esophageal squamous cell carcinoma (ESCC). and for who, in the judgement of the investigator, no standard alternative therapy is available or is not in the best interest of the participant. 3. Dose escalation Part 1C: - Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic CRC. - Participants with RAS-mutant and BRAF-mutant colorectal cancer are eligible for enrollment. 4. Dose expansion/optimization Part 2: Cancer diagnosis: - Participants in Cohorts A1 and A2 (Part 2A): Histologically or cytologically confirmed diagnosis of metastatic NSCLC. - Participants in Cohort B (Part 2A): Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic HCC, or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants (participants without cirrhosis must have had histological confirmation of diagnosis). - Participants in Cohorts C1 and C2 (Part 2A): - - Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic gastric cancer (GC) or Siewert Type 2 & 3 gastro esophageal junction (GEJ) adenocarcinoma. - - Disease with any combined positivity score (CPS) scoring. No need for CPS determination at local laboratory. - - Participants must have metastatic microsatellite instability (MSI) or mismatch repair (MMR) status known or determined locally and must have non-MSI-H or proficient MMR (pMMR) disease to be eligible. - - Participants with unknown human epidermal growth factor receptor 2 (HER2)/neu status must have their HER2/neu status determined locally. Participants with HER2/neu negative are eligible. Participants with HER2/neu positive tumors must have documentation of disease progression on treatment containing an approved HER2 targeted therapy to be eligible. - Participants in Part 2A Cohorts E1 and E2, Part 2B Cohort E3 and Part 2D Cohorts H1 and H2: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic CRC. - Participants in Part 2A Cohorts E1, and E2 and Part 2B Cohort E3 MSI status: Participants must have MSI status known or determined locally and must have non-MSI-H disease to be eligible. - Participants in Part 2A Cohorts E1, E2, Part 2B Cohort E3 and Part 2D Cohorts H1 and H2: Participants with RAS-mutant and BRAF-mutant CRC are eligible for enrollment. - Part 2C Cohorts G1, G2 and G3: Participants with histologically confirmed unresectable locally advanced or metastatic melanoma. 5. Prior anticancer therapy (For dose expansion/optimization Part 2 only): - Participants in Cohorts A1 and A2: Participants must have received at least 1 systemic therapy for the metastatic setting and must not be amenable to the available standard of care (SOC). - Participants in Cohort B: Participants who have received at least 1 prior anticancer therapy, including an anti-programmed cell de
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. - Predicted life expectancy 10 mg prednisone/day or an anti-inflammatory equivalent) within 1 week prior to the first dose of the study medicine. - Any clinically significant cardiac (including valvular) or vascular (thromboembolic disorders) disease, within 6 months prior to the first investigational medicinal product administration. - Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related AEs. - Has a known history or any evidence of interstitial lung disease or active, non-infectious pneumonitis within 3 years prior to the first dose of the study drug. - Organ transplant requiring immunosuppressive treatment. - Uncontrolled or active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or has a diagnosis of immunodeficiency. NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Dose escalation part 1A, 1C and Japan Cohort F: Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2 [Time Frame: Cycles 1 & 2 - 14 day per cycle] DLTs will be defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or American Society for Transplantation and Cellular Therapy (ASTCT) criteria for cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). 2. Dose escalation part 1B: Presence of DLTs in Cycle 1 to 3 in part B [Time Frame: Cycle 1 to 3 -14 days per cycle] 3. Dose escalation and Japan Cohort F: Percentage of participants experiencing treatment-emergent adverse events (TEAEs) [Time Frame: The time from the first dose of study interventions up to 30 days after last dose of study interventions] Presence of TEAEs, serious adverse events (SAEs), and lab abnormalities, according to the NCI CTCAE version 5.0 and ASTCT consensus grading. 4. Dose expansion/optimization: Objective response rate (ORR) [Time Frame: From baseline to the end of dose expansion/optimization (up to 2 years)] Proportion of participants who have a confirmed complete response (CR) or a partial response (PR), as the best overall response (BOR) determined by the Investigator as per the RECIST v1.1. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Dose escalation and Japan Cohort F: ORR [Time Frame: From baseline to the end of dose escalation (up to 2 years)] Proportion of participants who have a confirmed CR or a PR, as the BOR determined by the Investigator as per the RECIST v1.1. 2. Dose escalation, expansion/optimization and Japan Cohort F: Duration of response (DoR) [Time Frame: From baseline to the end of study (up to 2 years)] DoR is defined as the time from first documented evidence of confirmed CR or PR until progressive disease (PD) determined by Investigator per RECIST 1.1 or death from any cause, whichever occurs first. 3. Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Cmax [Time Frame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)] Maximum plasma concentration observed. 4. Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 AUCtau [Time Frame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)] Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T). 5. Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Tmax [Time Frame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)] First time to reach Cmax. 6. Dose escalation, expansion/optimization in Combination: Assessment of combined therapies Ctrough [Time Frame: Day 1 of each cycle to cycle 4 (cycle duration of 14 days)] 7. Dose escalation, expansion/optimization and Japan Cohort F: Percentage of participants with presence of anti-drug antibodies (ADAs) against SAR445877 [Time Frame: From the first dose of Cycle 1 to 30 days after last dose of study interventions (cycle duration of 14 days)] 8. Dose escalation, expansion/optimization: Percentage of participants with presence of ADAs against ADG126 [Time Frame: From the first dose of Cycle 1 to 30 days after last dose of study interventions (cycle duration of 14 days)] 9. Dose expansion/optimization: Time | — |
Countries
Chile, Israel, Japan, Netherlands, Spain, United States
Contacts
Public ContactUnit Clinical
Sanofi K.K.
Outcome results
None listed