Study of SAR444881 Administered Alone and in Combination With Other Therapeutics in Participants With Advanced Solid Tumors

NCT ID: NCT04717375

Last Updated: 2025-08-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-11
• Study Completion Date: 2025-07-02

Brief Summary

The study will enroll advanced cancer patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy. The study will be comprised of two parts - a dose escalation phase (Part 1) and a dose optimization/expansion phase (Part 2). Part 1 is comprised of three sub-parts: SAR444881 administered alone (Sub-Part 1A), SAR444881 administered in combination with pembrolizumab (Sub-Part 1B), and SAR444881 administered in combination with cetuximab (Sub-Part 1C). Part 2 is composed of two sub-parts: a dose optimization part where up to two doses of SAR444881 per indication are administered in combination with pembrolizumab, cetuximab, and/or carboplatin and pemetrexed (Sub-Part 2A); and a dose expansion part where SAR444881 is administered alone (Sub-Part 2B). In Sub-Part 2A, a two-stage design will be implemented to conduct dose optimization for each indication with combination therapy- Stage 1 (Preliminary Assessment) and Stage 2 (Randomization). Study is non-randomized except Stage 2 of Sub-Part 2A which will use randomization.

Detailed Description

Estimated Study Duration:

Dose Escalation (Part 1): Approximately 34 months Dose Optimization/Expansion (Part 2): Approximately 28 months

Conditions

Cancer; Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SAR444881 Dose Escalation (Sub-Part 1A)

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 will be administered intravenously (IV), every 2 weeks (Q2W).

Group Type: EXPERIMENTAL

SAR444881

Intervention Type: DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

SAR444881 in Combination with Pembrolizumab Dose Escalation (Sub-Part 1B)

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and pembrolizumab will be administered intravenously (IV), every 3 weeks (Q3W).

Group Type: EXPERIMENTAL

SAR444881

Intervention Type: DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Pembrolizumab

Intervention Type: DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

SAR444881 in Combination with Cetuximab Dose Escalation (Sub-Part 1C)

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and cetuximab will be administered intravenously (IV), every 2 weeks (Q2W).

Group Type: EXPERIMENTAL

SAR444881

Intervention Type: DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Cetuximab

Intervention Type: DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

SAR444881 Dose Optimization (Sub-Part 2A)

SAR444881 Dose Optimization in combination with pembrolizumab/carboplatin/pemetrexed, pembrolizumab, or cetuximab. The indication for the combination cohorts will be non-squamous non-small cell lung cancer (NSCLC), gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), colorectal carcinoma (CRC) any RAS. Enrollment will start after the recommended dose(s) of SAR444881 have been determined based on data from Sub-Parts 1A, 1B, and 1C.

Group Type: EXPERIMENTAL

SAR444881

Intervention Type: DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Pembrolizumab

Intervention Type: DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Cetuximab

Intervention Type: DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Carboplatin

Intervention Type: DRUG

Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

Pemetrexed

Intervention Type: DRUG

Pharmaceutical form: Powder for concentrate for solution for infusion or concentrate for solution for infusion; Route of administration: Intravenous

SAR444881 Dose Expansion (Sub-Part 2B)

The indication for this monotherapy cohort is cholangiocarcinoma. Enrollment will be opened based on emerging data from the dose-escalation phase and combination optimization data.

Group Type: EXPERIMENTAL

SAR444881

Intervention Type: DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Interventions

SAR444881

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Intervention Type: DRUG

Pembrolizumab

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Intervention Type: DRUG

Cetuximab

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Intervention Type: DRUG

Carboplatin

Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

Intervention Type: DRUG

Pemetrexed

Pharmaceutical form: Powder for concentrate for solution for infusion or concentrate for solution for infusion; Route of administration: Intravenous

Intervention Type: DRUG

Other Intervention Names

BND-22

Eligibility Criteria

Inclusion Criteria

• Patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy
• Histologic confirmation of malignancy
• Measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
• Participants must have adequate organ function as defined by laboratory tests
• Part 1: Following tumor types: Breast cancer, cervical cancer, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, hepatobiliary cancers (hepatocellular carcinoma (HCC), gallbladder cancer, cholangiocarcinoma), non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the skin, pancreatic adenocarcinoma, ovarian cancer or urothelial carcinoma
• Part 2: Following tumor types: Squamous cell carcinoma of the head and neck, Gastric or gastroesophageal junction adenocarcinoma, non-squamous non-small cell lung cancer, non-small cell lung cancer, colorectal carcinoma (CRC) any RAS, and/or Cholangiocarcinoma

Exclusion Criteria

• Active, known or suspected autoimmune disease
• Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
• Brain or leptomeningeal metastases
• Known history of positive test for HIV
• Non-HCC patients: acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV); HCC patients: untreated active HBV or dual infection with HBV/HCV
• Participants after solid organ or allogeneic hematopoietic stem cell transplant
• History of life-threatening toxicity related to prior immune therapy
• History of life-threatening toxicity related to prior cetuximab or other anti-EGFR antibodies (for Sub-Part 1C)
• Unstable or deteriorating cardiovascular disease within the previous 6 months
• Any major surgery within 4 weeks of study drug administration
• Prior/Concomitant Therapy:
• Cytotoxic/Non-cytotoxic anti-cancer agents, unless at least 4 weeks have elapsed from last dose
• Use of other investigational drugs within 28 days
• Prior treatment with macrophage or natural killer (NK) cells activating therapies
• Administration of a live attenuated vaccine within 28 days

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Mayo Clinic Hospital- Site Number : 8400003

Phoenix, Arizona, United States

City of Hope Comprehensive Cancer Center- Site Number : 8400002

Duarte, California, United States

University of Colorado- Site Number : 8400012

Aurora, Colorado, United States

Smilow Cancer Center at Yale-New Haven- Site Number : 8400001

New Haven, Connecticut, United States

Clermont Oncology Center- Site Number : 8400005

Clermont, Florida, United States

Mid Florida Hematology and Oncology Center- Site Number : 8400006

Orange City, Florida, United States

Mercy Cancer Center - MercyOne Richard Deming Cancer Center- Site Number : 8400011

Des Moines, Iowa, United States

Norton Cancer Institute - Downtown Women's Cancer Center- Site Number : 8400004

Louisville, Kentucky, United States

Mayo Clinic Hospital Rochester- Site Number : 8400007

Rochester, Minnesota, United States

Investigational Site Number : 1240001

Barrie, Ontario, Canada

Investigational Site Number : 1240003

Sherbrooke, Quebec, Canada

Investigational Site Number : 3760004

Haifa, , Israel

Investigational Site Number : 3760005

Jerusalem, , Israel

Investigational Site Number : 3760001

Petah Tikva, , Israel

Investigational Site Number : 3760003

Ramat Gan, , Israel

Investigational Site Number : 3760002

Tel Aviv, , Israel

Investigational Site Number : 8260003

London, London, City of, United Kingdom

Investigational Site Number : 8260002

Leeds, , United Kingdom

Countries

United States; Canada; Israel; United Kingdom

References

Mandel I, Haves Ziv D, Goldshtein I, Peretz T, Alishekevitz D, Fridman Dror A, Hakim M, Hashmueli S, Friedman I, Sapir Y, Greco R, Qu H, Nestle F, Wiederschain D, Pao L, Sharma S, Ben Moshe T. BND-22, a first-in-class humanized ILT2-blocking antibody, promotes antitumor immunity and tumor regression. J Immunother Cancer. 2022 Sep;10(9):e004859. doi: 10.1136/jitc-2022-004859.

Reference Type: DERIVED

PMID: 36096532 (View on PubMed)

Other Identifiers

BND-22-001

Identifier Type: OTHER

Identifier Source: secondary_id

U1111-1277-4421

Identifier Type: OTHER

Identifier Source: secondary_id

2023-504937-30-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

TCD17465

Identifier Type: -

Identifier Source: org_study_id