Recruiting
Phase 1
Phase 2

SAR445877

Sponsor:

Sanofi

Code:

NCT05584670

Conditions

Solid Tumor

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

SAR445877

Cetuximab

ADG126

Bevacizumab

Nivolumab

Study Details

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.

Conditions

Solid Tumor

Study ID

NCT05584670

Start date

Nov 29, 2022

Status verified date

Jun, 2026

Completion date

Jun 28, 2028

Anticipated

Primary completion date

Jan 19, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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/Exclusion criteria may apply.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Study Design

Enrollment

542 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: SAR445877 Escalation Phase (Part 1A)

SAR445877 monotherapy will be administered intravenously in participants with solid tumors over a 14-day cycle.

experimental: SAR445877 Escalation Phase (Part1B)

SAR445877 will be administered intravenously in combination with ADG126 in participants with advanced unresectable or metastatic melanoma, non-small cell lung cancer (NSCLC); renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), colorectal cancer (MSIH/dMMR), malignant pleural mesothelioma or esophageal squamous cell carcinoma (ESCC).

experimental: SAR445877 Escalation Phase (Part 1C)

SAR445877 will be administered intravenously in combination with bevacizumab in participants with metastatic colorectal cancer (CRC).

experimental: SAR445877 Expansion/Optimization Phase: Cohort A1 (Part 2A)

SAR445877 monotherapy will be administered intravenously (IV) in participants with non-small cell lung cancer (NSCLC).

experimental: SAR445877 Expansion/Optimization Phase: Cohort A2 (Part 2A)

SAR445877 monotherapy will be administered intravenously (IV) in participants with non-small cell lung cancer (NSCLC).

experimental: SAR445877 Expansion/Optimization Phase: Cohort B (Part 2A)

SAR445877 monotherapy will be administered intravenously in participants with hepatocellular carcinoma (HCC).

experimental: SAR445877 Expansion/Optimization Phase: Cohort C1 (Part 2A)

SAR445877 monotherapy will be administered intravenously in participants with gastric cancer/gastro esophageal junction adenocarcinoma (GC/GEJ).

experimental: SAR445877 Expansion/Optimization Phase: Cohort C2 (Part 2A)

SAR445877 monotherapy will be administered intravenously in participants with gastric cancer/gastro esophageal junction adenocarcinoma (GC/GEJ).

experimental: SAR445877 Expansion/Optimization Phase: Cohort D (Part 2A)

SAR445877 monotherapy will be administered intravenously IV in participants with immune infiltrated tumor type.

experimental: SAR445877 Expansion/Optimization Phase: Cohort E1 (Part 2B)

SAR445877 monotherapy will be administered intravenously in participants with colorectal cancer (CRC).

experimental: SAR445877 Expansion/optimization Phase: Cohort E2 (Part 2A)

SAR445877 monotherapy will be administered intravenously in participants with colorectal cancer (CRC).

experimental: SAR445877 Expansion/optimization Phase: Cohort E3 (Part 2B)

SAR445877 will be administered intravenously in combination with cetuximab in participants with colorectal cancer.

experimental: SAR445877 Japan Cohort F

SAR445877 monotherapy will be administered intravenously in participants with advanced unresectable or metastatic solid tumor, from Japan.

experimental: SAR445877 Expansion/Optimization Phase Cohort G1 (Part 2C)

SAR445877 will be administered intravenously in combination with ADG126 in participants with metastatic melanoma.

experimental: SAR445877 Expansion/Optimization Phase Cohort G2 (Part 2C)

SAR445877 will be administered intravenously in combination with ADG126 in participants with metastatic melanoma.

experimental: SAR445877 Expansion/Optimization Phase Cohort G3 (Part 2C)

The Standard of Care (nivolumab and ipilimumab) will be administered intravenously in participants with metastatic melanoma.

experimental: SAR445877 Expansion/Optimization Phase Cohort H1 (Part 2D)

SAR445877 will be administered intravenously in combination with bevacizumab in participants with advanced unresectable or metastatic CRC.

experimental: SAR445877 Expansion/Optimization Phase Cohort H2 (Part 2D)

SAR445877 will be administered intravenously in combination with bevacizumab in participants with advanced unresectable or metastatic CRC.

Interventions

SAR445877

Concentrate for solution for infusion

Cetuximab

Solution for infusion

ADG126

Solution for infusion

Bevacizumab

Solution for infusion

Nivolumab

Solution for infusion

Ipilimumab

Solution for infusion

Primary outcome measure

  • 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 days per cycle ]
  • Dose escalation part 1B: Presence of dose-limiting toxicities (DLTs) in Cycle 1 to 3 in part B [ Time Frame: Cycle 1 to 3 -14 days per cycle ]
  • 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 ]
  • Dose expansion/optimization: Objective response rate (ORR) [ Time Frame: From baseline to the end of dose expansion/optimization (up to 2 years) ]

Central Contacts and Locations

Central contacts

Trial Transparency email recommended (Toll free for US & Canada)

800-633-1610contact-us@sanofi.com

Locations

Christiana Care Health System - Newark- Site Number : 8400011

Recruiting

Newark, Delaware, United States, 19718

Contacts

Jamal Misleh

302-366-1200Jamal.misleh@usoncology.com

Principal Investigator:

Jamal Misleh

University of Iowa- Site Number : 8400014

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Muhammad Furquan

319-356-1527muhammad-furqan@uiowa.edu

Principal Investigator:

Muhammad Furquan

The University of Kansas Cancer Center - Westwood- Site Number : 8400008

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Lisa Bogart

913-945-7552CTNurseNav@kumc.edu

Principal Investigator:

Joaquina Baranda

Karmanos Cancer Institute - Detroit- Site Number : 8400006

Recruiting

Detroit, Michigan, United States, 48201

Contacts

Ammar Sukari

313-576-8751sukaria@karmanos.org

Principal Investigator:

Ammar Sukari

John Theurer Cancer Center- Site Number : 8400001

Recruiting

Hackensack, New Jersey, United States, 07601

Contacts

Suzanne Kosky

551-996-3986suzanne.kosky@hmhn.org

Principal Investigator:

Martin Gutierrez

NYU Langone Medical Center- Site Number : 8400013

Recruiting

New York, New York, United States, 10016

Contacts

Paul Oberstein

212-731-6120paul.oberstein@nyulangone.org

Principal Investigator:

Paul Oberstein

Rhode Island Hospital - Providence - Eddy Street- Site Number : 8400004

Recruiting

Providence, Rhode Island, United States, 02905

Contacts

Kaitlyn Krar

401-444-4818CKrar@Lifespan.org

Principal Investigator:

Khaldoun Almhanna

The University of Texas MD Anderson Cancer Center- Site Number : 8400005

Recruiting

Houston, Texas, United States, 77030

Contacts

Aung Naing

713-794-5555anaing@mdanderson.org

Principal Investigator:

Aung Naing

Fred Hutchinson Cancer Center- Site Number : 8400010

Recruiting

Seattle, Washington, United States, 98109

Contacts

Elena Chiorean

206-606-6248gchiorea@seattlecca.org

Principal Investigator:

Elena Chiorean

More Information

Sponsor

Sanofi

Last update posted

Jun 23, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Sanofi on 2026-06-23.