A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors

NCT ID: NCT05584670

Last Updated: 2025-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

542 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-29

Study Completion Date

2028-06-28

Brief Summary

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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

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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.

Conditions

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Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

Bevacizumab

Intervention Type DRUG

Solution for infusion

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.

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

Bevacizumab

Intervention Type DRUG

Solution for infusion

SAR445877 Escalation Phase (Part 1A)

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

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).

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

ADG126

Intervention Type DRUG

Solution for infusion

SAR445877 Escalation Phase (Part 1C)

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

Bevacizumab

Intervention Type DRUG

Solution for infusion

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

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

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

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

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

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

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).

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

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).

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

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

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

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

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

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

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

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

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

Cetuximab

Intervention Type DRUG

Solution for infusion

SAR445877 Japan Cohort F

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

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

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

ADG126

Intervention Type DRUG

Solution for infusion

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

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

Group Type EXPERIMENTAL

SAR445877

Intervention Type DRUG

Concentrate for solution for infusion

ADG126

Intervention Type DRUG

Solution for infusion

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

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Solution for infusion

Ipilimumab

Intervention Type DRUG

Solution for infusion

Interventions

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SAR445877

Concentrate for solution for infusion

Intervention Type DRUG

Cetuximab

Solution for infusion

Intervention Type DRUG

ADG126

Solution for infusion

Intervention Type DRUG

Bevacizumab

Solution for infusion

Intervention Type DRUG

Nivolumab

Solution for infusion

Intervention Type DRUG

Ipilimumab

Solution for infusion

Intervention Type DRUG

Other Intervention Names

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Erbitux bevacizumab-bvzr, Zirabev® Opdivo® Yervoy®

Eligibility Criteria

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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


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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Christiana Care Health System- Site Number : 8400011

Newark, Delaware, United States

Site Status RECRUITING

University of Iowa- Site Number : 8400014

Iowa City, Iowa, United States

Site Status RECRUITING

University of Kansas Cancer Center Clinical Research Center (Fairway) Site Number : 8400008

Fairway, Kansas, United States

Site Status RECRUITING

Barbara Ann Karmanos Cancer Institute - Detroit- Site Number : 8400006

Detroit, Michigan, United States

Site Status RECRUITING

John Theurer Cancer Center Site Number : 8400001

Hackensack, New Jersey, United States

Site Status RECRUITING

NYU Langone Medical Center-New York- 550 1st Ave - BRANY - PPDS- Site Number : 8400013

New York, New York, United States

Site Status RECRUITING

Rhode Island Hospital Site Number : 8400004

Providence, Rhode Island, United States

Site Status RECRUITING

University of Texas MD Anderson Cancer Center Site Number : 8400005

Houston, Texas, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center - 825 Eastlake Ave E- Site Number : 8400010

Seattle, Washington, United States

Site Status RECRUITING

Servicios Médicos URUMED SpA_Investigational Site Number : 1520002

Rancagua, General Bernardo O'Higgins, Chile

Site Status RECRUITING

BIOCINETIC Ltda_Investigational Site Number : 1520008

Santiago, Reg Metropolitana de Santiago, Chile

Site Status RECRUITING

Fundacion Arturo Lopez Perez (FALP) - Providencia - Jose Manuel Infante 805_Investigational Site Number : 1520007

Providencia, , Chile

Site Status RECRUITING

Centro de Investigacion Clinica Bradford Hill_Investigational Site Number : 1520004

Recoleta, , Chile

Site Status RECRUITING

Hadassah Medical Center - PPDS_Investigational Site Number : 3760005

Jerusalem, Jerusalem, Israel

Site Status RECRUITING

Shamir Medical Center_Investigational Site Number : 3760004

Be’er Ya‘aqov, , Israel

Site Status RECRUITING

Sheba Medical Center - PPDS_Investigational Site Number : 3760003

Ramat Gan, , Israel

Site Status RECRUITING

Tel Aviv Sourasky Medical Center Ichilov - PPDS_Investigational Site Number : 3760001

Tel Aviv, , Israel

Site Status RECRUITING

Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis_Investigational Site Number : 5280001

Amsterdam, North Holland, Netherlands

Site Status RECRUITING

Erasmus MC_Investigational Site Number : 5280003

Rotterdam, South Holland, Netherlands

Site Status RECRUITING

Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON_Investigational Site Number : 7240007

Barcelona, , Spain

Site Status RECRUITING

START MADRID_Hospital Universitario HM Sanchinarro - CIOCC_Investigational Site Number : 7240005

Madrid, , Spain

Site Status RECRUITING

Countries

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United States Chile Israel Netherlands Spain

Central Contacts

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

Role: CONTACT

Phone: 800-633-1610

Email: [email protected]

Facility Contacts

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Jamal Misleh

Role: primary

Muhammad Furquan

Role: primary

Lisa Bogart

Role: primary

Ammar Sukari

Role: primary

Suzanne Kosky

Role: primary

Paul Oberstein

Role: primary

Kaitlyn Krar

Role: primary

Aung Naing

Role: primary

Elena Chiorean

Role: primary

Plinio Fernandez

Role: primary

Nicolas Obando Martínez

Role: primary

Christian Caglevic Medina

Role: primary

Carlos Ignacio Rojas Garcia

Role: primary

Jonathan Cohen

Role: primary

Carmell Fink

Role: primary

Tamar Beller

Role: primary

Ravit Geva

Role: primary

Marloes van Dongen

Role: primary

Ferry Eskens

Role: primary

Elena Garralda

Role: primary

Emiliano Calvo

Role: primary

Related Links

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Other Identifiers

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U1111-1277-4827

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-507141-28

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-001239-95

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TCD17620

Identifier Type: -

Identifier Source: org_study_id