A Phase 1/2, open label, first-in-human, dose escalation and expansion study for the evaluation of safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of SAR445877 administered as monotherapy or in combination with other anticancer therapies in adults with advanced solid tumors
A first-in-human, dose escalation and dose expansion study of SAR445877 in adult participants with advanced solid tumors
Obara Kentaro
Sanofi K.K.
Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
+81-3-6301-3670
clinical-trials-jp@sanofi.com
Clinical Study Unit
Sanofi K.K.
Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
+81-3-6301-3670
clinical-trials-jp@sanofi.com
Not Recruiting
Dec. 01, 2025
Jan. 06, 2026
473
Interventional
randomized controlled trial
open(masking not used)
uncontrolled control
single assignment
treatment purpose
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 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.
4. 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 death 1 (PD1)/programmed cell death-ligand 1 (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 SOC.
- 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-epidermal growth factor receptor (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 SOC treatment option or decline or is intolerant to be treated with SOC treatment.
Measurable Disease:
- At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria.
Part 2D: Adequate coagulation function for all participants. For participants receiving anti-coagulant therapy (except platelet anti-aggregates) the adequate therapeutic levels of international normalized ratio (INR) should be confirmed.
Capable of giving signed informed consent.
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 <=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) adverse events (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 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.
18age old over
No limit
Both
Solid tumor
Drug: SAR445877, Pharmaceutical form: Concentrate for solution for infusion
Drug: Cetuximab (Erbitux), Pharmaceutical form: Solution for infusion
Drug: ADG126, Pharmaceutical form: Solution for infusion
Drug: Bevacizumab (Zirabev), Pharmaceutical form: Solution for infusion
Drug: Nivolumab (Opdivo), Pharmaceutical form: Solution for infusion
Drug: Ipilimumab (Yervoy), Pharmaceutical form: Solution for infusion
Study Arms:
Experimental: SAR445877 Escalation Phase (Part 1A)
- SAR445877 monotherapy will be administered intravenously (IV) in participants with solid tumors over a 14-day cycle.
- Interventions: SAR445877
Experimental: SAR445877 Escalation Phase (Part 1B)
- SAR445877 will be administered IV in combination with ADG126 in participants with advanced unresectable or metastatic melanoma, NSCLC, RCC, HCC, CRC (MSI-H/dMMR), malignant pleural mesothelioma or ESCC.
- Interventions: SAR445877, ADG126
Experimental: SAR445877 Expansion/Optimization Phase: Cohort A1 (Part 2A)
- SAR445877 monotherapy will be administered IV in participants with NSCLC.
- Interventions: SAR445877
Experimental: SAR445877 Expansion/Optimization Phase: Cohort A2 (Part 2A)
- SAR445877 monotherapy will be administered IV in participants with NSCLC.
- Interventions: SAR445877
Experimental: SAR445877 Expansion/Optimization Phase: Cohort B (Part 2A)
- SAR445877 monotherapy will be administered IV in participants with HCC.
- Interventions: SAR445877
Experimental: SAR445877 Expansion/Optimization Phase: Cohort C1 (Part 2A)
- SAR445877 monotherapy will be administered IV in participants with GC/GEJ adenocarcinoma.
- Interventions: SAR445877
Experimental: SAR445877 Expansion/Optimization Phase: Cohort C2 (Part 2A)
- SAR445877 monotherapy will be administered IV in participants with GC/GEJ adenocarcinoma.
- Interventions: SAR445877
Experimental: SAR445877 Expansion/Optimization Phase: Cohort D (Part 2A)
- SAR445877 monotherapy will be administered IV in participants with immune infiltrated tumor type.
- Interventions: SAR445877
Experimental: SAR445877 Expansion/Optimization Phase: Cohort E1 (Part 2A)
- SAR445877 monotherapy will be administered IV in participants with CRC.
- Interventions: SAR445877
Experimental: SAR445877 Expansion/Optimization Phase: Cohort E2 (Part 2A)
- SAR445877 monotherapy will be administered IV in participants with CRC.
- Interventions: SAR445877
Experimental: SAR445877 Expansion/Optimization Phase: Cohort E3 (Part 2B)
- SAR445877 will be administered IV in combination with cetuximab in participants with CRC.
- Interventions: SAR445877, Cetuximab
Experimental: SAR445877 Japan Cohort F
- SAR445877 monotherapy will be administered IV in participants with advanced unresectable or metastatic solid tumor, from Japan.
- Interventions: SAR445877
Experimental: SAR445877 Expansion/Optimization Phase: Cohort G1 (Part 2C)
- SAR445877 will be administered IV in combination with ADG126 in participants with metastatic melanoma.
- Interventions: SAR445877, ADG126
Experimental: SAR445877 Expansion/Optimization Phase: Cohort G2 (Part 2C)
- SAR445877 will be administered IV in combination with ADG126 in participants with metastatic melanoma.
- Interventions: SAR445877, ADG126
Experimental: SAR445877 Expansion/Optimization Phase: Cohort G3 (Part 2C)
- The SOC (nivolumab and ipilimumab) will be administered IV in participants with metastatic melanoma.
- Interventions: nivolumab, ipilimumab
Experimental: SAR445877 Expansion/Optimization Phase: Cohort H1 (Part 2D)
- SAR445877 will be administered IV in combination with bevacizumab in participants with advanced unresectable or metastatic CRC.
- Interventions: SAR445877, bevacizumab
Experimental: SAR445877 Expansion/Optimization Phase: Cohort H2 (Part 2D)
- SAR445877 will be administered IV in combination with bevacizumab in participants with advanced unresectable or metastatic CRC.
- Interventions: SAR445877, bevacizumab
1. Dose escalation part 1A 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 Cycles 1 to 3
DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or immune effector cell-associated neurotoxicity syndrome (ICANS)
[Time Frame: Cycles 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.
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 to response
[Time Frame: 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 to the first documented evidence of confirmed PR or CR determined by Investigator per RECIST 1.1.
10. Dose expansion/optimization: Clinical Benefit Rate
[Time Frame: 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.
11. Dose expansion/optimization: Progression-free survival (PFS)
[Time Frame: 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 investigational medicinal product 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.
12. Dose expansion/optimization: Overall survival (OS)
[Time Frame: From baseline to end of dose expansion/optimization (up to 2 years)]
OS is defined as the time from the first dose of investigational medicinal product to the date of death due to any cause.
13. Dose expansion/optimization: Number of participants with AEs
[Time Frame: The time from the first dose of study interventions up to 30 days after last dose of study interventions]
Presence of AEs graded according to the NCI CTCAE v5.0 or ASTCT consensus grading.
Sanofi K.K.
National Cancer Center Institutional Review Board
5-1-1 Tsukiji, Chuo-ku, Tokyo, Tokyo
Approval
Nov. 26, 2025
Yes
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
