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

NCT05584670 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: TCD17620U1111-1277-48272023-507141-282022-001239-95
• Study Type: interventional
• Target: 542
• Locations: 6 countries
• Sites: 22

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

Outcome Measures

Primary Outcomes (4)

• Dose escalation part 1A, 1C and Japan Cohort F: Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2

  DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or immune effector cell-associated neurotoxicity syndrome (ICANS)

  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

  Cycle 1 to 3 -14 days per cycle

• Dose escalation and Japan Cohort F: Percentage of participants experiencing treatment-emergent adverse events (TEAEs)

  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

  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)

  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

  From baseline to the end of dose expansion/optimization (up to 2 years)

Secondary Outcomes (13)

• Dose escalation and Japan Cohort F: Objective response rate (ORR)

  From baseline to the end of dose escalation (up to 2 years)

• Dose escalation, expansion/optimization and Japan Cohort F: Duration of response (DoR)

  From baseline to the end of study (up to 2 years)

• 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)

• 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)

• 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)

Study Arms (18)

SAR445877 Escalation Phase (Part 1A)

EXPERIMENTAL

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

Drug: SAR445877

SAR445877 Escalation Phase (Part1B)

EXPERIMENTAL

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).

Drug: SAR445877; Drug: ADG126

SAR445877 Escalation Phase (Part 1C)

EXPERIMENTAL

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

Drug: SAR445877; Drug: Bevacizumab

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

EXPERIMENTAL

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

Drug: SAR445877

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

EXPERIMENTAL

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

Drug: SAR445877

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

EXPERIMENTAL

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

Drug: SAR445877

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

EXPERIMENTAL

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

Drug: SAR445877

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

EXPERIMENTAL

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

Drug: SAR445877

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

EXPERIMENTAL

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

Drug: SAR445877

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

EXPERIMENTAL

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

Drug: SAR445877

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

EXPERIMENTAL

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

Drug: SAR445877

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

EXPERIMENTAL

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

Drug: SAR445877; Drug: Cetuximab

SAR445877 Japan Cohort F

EXPERIMENTAL

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

Drug: SAR445877

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

EXPERIMENTAL

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

Drug: SAR445877; Drug: ADG126

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

EXPERIMENTAL

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

Drug: SAR445877; Drug: ADG126

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

EXPERIMENTAL

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

Drug: Nivolumab; Drug: Ipilimumab

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

EXPERIMENTAL

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

Drug: SAR445877; Drug: Bevacizumab

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

EXPERIMENTAL

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

Drug: SAR445877; Drug: Bevacizumab

Interventions

SAR445877 DRUG

Concentrate for solution for infusion

SAR445877 Escalation Phase (Part 1A); SAR445877 Escalation Phase (Part 1C); SAR445877 Escalation Phase (Part1B); SAR445877 Expansion/Optimization Phase Cohort G1 (Part 2C); SAR445877 Expansion/Optimization Phase Cohort G2 (Part 2C); SAR445877 Expansion/Optimization Phase Cohort H1 (Part 2D); SAR445877 Expansion/Optimization Phase Cohort H2 (Part 2D); SAR445877 Expansion/Optimization Phase: Cohort A1 (Part 2A); SAR445877 Expansion/Optimization Phase: Cohort A2 (Part 2A); SAR445877 Expansion/Optimization Phase: Cohort B (Part 2A); SAR445877 Expansion/Optimization Phase: Cohort C1 (Part 2A); SAR445877 Expansion/Optimization Phase: Cohort C2 (Part 2A); SAR445877 Expansion/Optimization Phase: Cohort D (Part 2A); SAR445877 Expansion/Optimization Phase: Cohort E1 (Part 2B); SAR445877 Expansion/optimization Phase: Cohort E2 (Part 2A); SAR445877 Expansion/optimization Phase: Cohort E3 (Part 2B); SAR445877 Japan Cohort F

Cetuximab DRUG

Solution for infusion

Also known as: Erbitux

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

ADG126 DRUG

Solution for infusion

SAR445877 Escalation Phase (Part1B); SAR445877 Expansion/Optimization Phase Cohort G1 (Part 2C); SAR445877 Expansion/Optimization Phase Cohort G2 (Part 2C)

Bevacizumab DRUG

Solution for infusion

Also known as: bevacizumab-bvzr, Zirabev®

SAR445877 Escalation Phase (Part 1C); SAR445877 Expansion/Optimization Phase Cohort H1 (Part 2D); SAR445877 Expansion/Optimization Phase Cohort H2 (Part 2D)

Nivolumab DRUG

Solution for infusion

Also known as: Opdivo®

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

Ipilimumab DRUG

Solution for infusion

Also known as: Yervoy®

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (22)

Christiana Care Health System- Site Number : 8400011

Newark, Delaware, 19713-2072, United States

RECRUITING

University of Iowa- Site Number : 8400014

Iowa City, Iowa, 52242-1009, United States

RECRUITING

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

Fairway, Kansas, 66205-2528, United States

RECRUITING

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

Detroit, Michigan, 48201, United States

RECRUITING

John Theurer Cancer Center Site Number : 8400001

Hackensack, New Jersey, 07601, United States

RECRUITING

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

New York, New York, 10016-6402, United States

RECRUITING

Rhode Island Hospital Site Number : 8400004

Providence, Rhode Island, 02903, United States

RECRUITING

University of Texas MD Anderson Cancer Center Site Number : 8400005

Houston, Texas, 77030-4000, United States

RECRUITING

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

Seattle, Washington, 98109-4405, United States

RECRUITING

Servicios Médicos URUMED SpA_Investigational Site Number : 1520002

Rancagua, General Bernardo O'Higgins, 2852424, Chile

RECRUITING

BIOCINETIC Ltda_Investigational Site Number : 1520008

Santiago, Reg Metropolitana de Santiago, 8350595, Chile

RECRUITING

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

Providencia, 7500000, Chile

RECRUITING

Centro de Investigacion Clinica Bradford Hill_Investigational Site Number : 1520004

Recoleta, 8420391, Chile

RECRUITING

Hadassah Medical Center - PPDS_Investigational Site Number : 3760005

Jerusalem, Jerusalem, 91120, Israel

RECRUITING

Shamir Medical Center_Investigational Site Number : 3760004

Be’er Ya‘aqov, 70300, Israel

RECRUITING

Sheba Medical Center - PPDS_Investigational Site Number : 3760003

Ramat Gan, 5262100, Israel

RECRUITING

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

Tel Aviv, 6423906, Israel

RECRUITING

Investigational Site Number : 3920001

Kashiwa-Shi, 277-0882, Japan

RECRUITING

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

Amsterdam, North Holland, 1066 CX, Netherlands

RECRUITING

Erasmus MC_Investigational Site Number : 5280003

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

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

Barcelona, 08035, Spain

RECRUITING

START MADRID_Hospital Universitario HM Sanchinarro - CIOCC_Investigational Site Number : 7240005

Madrid, 28050, Spain

RECRUITING

Related Links

• TCD17620 Plain Language Results Summary

MeSH Terms

Interventions

Cetuximab; Bevacizumab; Nivolumab; Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2022
• First Posted: October 18, 2022
• Study Start: November 29, 2022
• Primary Completion (Estimated): January 19, 2027
• Study Completion (Estimated): June 28, 2028
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

JP (1); NL (2); IL (4); US (9); CL (4); ES (2)