Solid Tumor
Conditions
Brief summary
This is a Phase 1/2, open label, multiple cohort study to assess the safety and preliminary efficacy of SAR445877 as a monotherapy or in combination with other anticancer therapies for participants aged at least 18 years with advanced unresectable or metastatic solid tumors. The study will include 2 parts: A dose escalation Part 1: for finding the therapeutic dose(s) of SAR445877 in a monotherapy given every 2 weeks (Q2W) or weekly (QW) and in combination with other anticancer therapies when applicable. A multicohort dose expansion/dose optimization Part 2: for the assessment of safety and preliminary efficacy of SAR445877 in monotherapy and in combination with cetuximab or with next generation aCTLA4 (ADG126) or with bevacizumab. 2 recommended doses for expansion/optimization of SAR445877 identified from dose escalation part 1 will be tested in different indications in monotherapy and in combination with other anticancer therapies as applicable. Approximately 542 participants will be exposed to the study intervention: * approximately 123 participants in part 1, * up to 410 participants in expansion/dose optimization part (part 2) * and up to 9 participants in Japan cohort F.
Detailed description
The duration of the study for a participant will include: * Screening Period: up to 28 days * Treatment Period: enrolled and exposed participants will receive continuous treatment until progressive disease (PD), or an occurrence of an unacceptable AE, a withdrawal of consent, or until other permanent discontinuation criteria described in the protocol are met. The End of Treatment (EOT) visit will occur 30 days ±7 days from the last IMP administration or prior to the initiation of further therapy, whichever occurs first. The follow-up period will occur until disease progression, the start of new anticancer therapy, death, or withdrawal of participant's consent, whichever comes first.
Interventions
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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, NSCLC; renal cell carcinoma (RCC); HCC, colorectal cancer (MSI-H/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 colorectal cancer * 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 non-small cell lung cancer (NSCLC) * Participants in Cohort B (part 2A): Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic hepatocellular carcinoma (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 CPS scoring. No need for CPS determination at local laboratory * Participants must have MSI (metastatic microsatellite instability) or MMR (mismatch repair) status known or determined locally and must have non-MSI-H or proficient MMR (pMMR) disease to be eligible. * Participants with unknown 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 colorectal cancer. * 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 colorectal cancer 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 SOC. * Participants in Cohort B: Participants who have received at least 1 prior anticancer therapy, including an anti-PD1/PD-L1 containing regimen, and for whom have progressed after a primary or secondary resistance to an anti-PD1/PD-L1. * Participants in Cohorts C1 and C2: Participants should have failed or relapsed after at least 1 prior line of treatment which may or may not include an anti-PD1/PD-L1-based treatment depending on local standard of care. * Participants in Cohort D: Participants must have received at least 1 systemic therapy for their advanced/ metastatic setting and must not be amenable to the available SOC. * Participants in Part 2A Cohorts E1 and E2 and Part 2D Cohorts H1 and H2 should have failed or relapsed on at least 2 prior regimens. * Participants in cohort E3 should have failed or relapsed on at least 1 prior regimen. Participants who have received cetuximab or other anti-EGFR therapy as part of their prior line of treatment are eligible. * Part 2C Cohorts G1, G2 and G3: Participants must have received at least one prior line of therapy for advanced/metastatic melanoma and/or does not have any standard of care (SoC) treatment option or decline or is intolerant to be treated with SoC treatment. Measurable Disease: * At least 1 measurable lesion per RECIST 1.1 criteria Part 1C and Part 2D: Adequate coagulation function for all participants. For participants receiving anti-coagulant therapy (except platelet anti-aggregates) the adequate therapeutic levels of INR should be confirmed. Capable of giving signed informed consent.
Exclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of ≥2 * Predicted life expectancy ≤3 months * For participants with HCC- Cohort B (Part 2): Child Pugh Class B or C liver score. Participants with Child Pugh Class B-7 score are allowed for Part 1. * Diagnosed of any other malignancies, either progressing or requiring active treatments, within 2 years prior to enrollment * Known active brain metastases or leptomeningeal metastases * History of treatment-related immune-mediated (or immune-related) AEs from immune-modulatory agents (including but not limited to anti-PD1/PD-L1 agents and anti-cytotoxic T lymphocyte associated protein 4 monoclonal antibodies) that caused permanent discontinuation of the agent, or that were Grade 4 in severity or have not resolved to Grade ≤1 * Has any condition requiring ongoing/continuous corticosteroid therapy (\>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 IMP 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 adverse events * 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose escalation part 1A, 1C and Japan Cohort F: Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2 | Cycles 1 & 2 - 14 days per cycle | DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or immune effector cell-associated neurotoxicity syndrome (ICANS) |
| Dose escalation part 1B: Presence of dose-limiting toxicities (DLTs) in Cycle 1 to 3 in part B | Cycle 1 to 3 -14 days per cycle | — |
| Dose escalation and Japan Cohort F: Percentage of participants experiencing treatment-emergent adverse events (TEAEs) | The time from the first dose of study interventions up to 30 days after last dose of study interventions | Presence of TEAEs, SAEs, and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading |
| Dose expansion/optimization: Objective response rate (ORR) | 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 Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose escalation and Japan Cohort F: Objective response rate (ORR) | From baseline to the end of dose escalation (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 Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
| Dose escalation, expansion/optimization and Japan Cohort F: Duration of response (DoR) | 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 |
| Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Cmax | Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days) | Maximum plasma concentration observed |
| Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 AUCtau | 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) |
| Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Tmax | Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days) | First time to reach Cmax |
| Dose escalation, expansion/optimization in Combination: Assessment of combined therapies Ctrough | Day 1 of each cycle to cycle 4 (cycle duration of 14 days) | — |
| Dose escalation, expansion/optimization and Japan Cohort F: Percentage of participants with presence of anti-drug antibodies (ADAs) against SAR445877 | From the first dose of Cycle 1 to 30 days after last dose of study interventions (cycle duration of 14 days) | — |
| Dose escalation, expansion/optimization: Percentage of participants with presence of anti-drug antibodies (ADAs) against ADG126 | From the first dose of Cycle 1 to 30 days after last dose of study interventions (cycle duration of 14 days) | — |
| Dose expansion/optimization: Time to response | From baseline to end of dose expansion/optimization (up to 2 years) | Time to response is defined as the time from the first administration of investigational medicinal product (IMP) to the first documented evidence of confirmed PR or CR determined by Investigator per RECIST 1.1 |
| Dose expansion/optimization: Clinical Benefit Rate | From baseline to end of dose expansion/optimization (up to 2 years) | Clinical Benefit Rate including confirmed CR or PR at any time or stable disease (SD) of at least 6 months determined by Investigator per RECIST 1.1 |
| Dose expansion/optimization: Progression-free survival | From baseline to end of dose expansion/optimization (up to 2 years) | PFS is defined as the time from the date of first administration of IMP to the date of the first documented disease progression determined by Investigator as per RECIST 1.1 or death from any cause, whichever occurs first |
| Dose expansion/optimization: Overall survival | From baseline to end of dose expansion/optimization (up to 2 years) | Overall survival (OS) is defined as the time from the first dose of IMP to the date of death due to any cause. |
| Dose expansion/optimization: Number of participants with Adverse events (AE) | The time from the first dose of study interventions up to 30 days after last dose of study interventions. | Presence of adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 or American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading |
Countries
Chile, Israel, Japan, Netherlands, Spain, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Outcome results
None listed