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

NCT04717375 | Terminated Phase 1 FDA Drug

• 4 other identifiers: TCD17465BND-22-001U1111-1277-44212023-504937-30-00
• Study Type: interventional
• Target: 125
• Locations: 4 countries
• Sites: 18

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.

Conditions

Cancer; Neoplasm

Outcome Measures

Primary Outcomes (3)

• Part 1: Incidence of treatment-emergent adverse events (TEAEs) dose limiting toxicities (DLT)

  Incidence of TEAEs meeting protocol defined DLT criteria

  Cycle 1 (28 days)

• Part 1: Incidence of treatment-emergent adverse events and serious adverse events

  Through study completion, an average of 5 months

• Part 2: Objective Response Rate (ORR) per RECIST v1.1

  Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1

  Through study completion, an average of 3 months

Secondary Outcomes (17)

• Part 1: Objective Response Rate (ORR) per RECIST v1.1

  Through study completion, an average of 3 months

• Part 1: Maximum observed plasma concentration [Cmax]

  Through study completion, an average of 2 months

• Part 1: Serum concentration at the end of the dosing interval (Ctrough)

  Through study completion, an average of 2 months

• Part 1: time of maximum observed serum concentration (Tmax)

  Through study completion, an average of 2 months

• Part 1: Terminal elimination half-life [T1/2]

  Through study completion, an average of 2 months

Study Arms (5)

SAR444881 Dose Escalation (Sub-Part 1A)

EXPERIMENTAL

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).

Drug: SAR444881

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

EXPERIMENTAL

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).

Drug: SAR444881; Drug: Pembrolizumab

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

EXPERIMENTAL

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).

Drug: SAR444881; Drug: Cetuximab

SAR444881 Dose Optimization (Sub-Part 2A)

EXPERIMENTAL

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.

Drug: SAR444881; Drug: Pembrolizumab; Drug: Cetuximab; Drug: Carboplatin; Drug: Pemetrexed

SAR444881 Dose Expansion (Sub-Part 2B)

EXPERIMENTAL

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.

Drug: SAR444881

Interventions

SAR444881 DRUG

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

Also known as: BND-22

SAR444881 Dose Escalation (Sub-Part 1A); SAR444881 Dose Expansion (Sub-Part 2B); SAR444881 Dose Optimization (Sub-Part 2A); SAR444881 in Combination with Cetuximab Dose Escalation (Sub-Part 1C); SAR444881 in Combination with Pembrolizumab Dose Escalation (Sub-Part 1B)

Pembrolizumab DRUG

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

SAR444881 Dose Optimization (Sub-Part 2A); SAR444881 in Combination with Pembrolizumab Dose Escalation (Sub-Part 1B)

Cetuximab DRUG

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

SAR444881 Dose Optimization (Sub-Part 2A); SAR444881 in Combination with Cetuximab Dose Escalation (Sub-Part 1C)

Carboplatin DRUG

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

SAR444881 Dose Optimization (Sub-Part 2A)

Pemetrexed DRUG

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

SAR444881 Dose Optimization (Sub-Part 2A)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (18)

Mayo Clinic Hospital- Site Number : 8400003

Phoenix, Arizona, 85054-4504, United States

Location

City of Hope Comprehensive Cancer Center- Site Number : 8400002

Duarte, California, 91030, United States

Location

University of Colorado- Site Number : 8400012

Aurora, Colorado, 80045, United States

Location

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

New Haven, Connecticut, 06511, United States

Location

Clermont Oncology Center- Site Number : 8400005

Clermont, Florida, 34711, United States

Location

Mid Florida Hematology and Oncology Center- Site Number : 8400006

Orange City, Florida, 32763, United States

Location

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

Des Moines, Iowa, 50314, United States

Location

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

Louisville, Kentucky, 40202, United States

Location

Mayo Clinic Hospital Rochester- Site Number : 8400007

Rochester, Minnesota, 55905, United States

Location

Investigational Site Number : 1240001

Barrie, Ontario, L4M 6M2, Canada

Location

Investigational Site Number : 1240003

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Investigational Site Number : 3760004

Haifa, 3109601, Israel

Location

Investigational Site Number : 3760005

Jerusalem, 9112001, Israel

Location

Investigational Site Number : 3760001

Petah Tikva, 4941492, Israel

Location

Investigational Site Number : 3760003

Ramat Gan, 5262100, Israel

Location

Investigational Site Number : 3760002

Tel Aviv, 6423906, Israel

Location

Investigational Site Number : 8260003

London, London, City of, W12 0HS, United Kingdom

Location

Investigational Site Number : 8260002

Leeds, LS9 7TF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 36096532 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab; Cetuximab; Carboplatin; Pemetrexed

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

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: January 15, 2021
• First Posted: January 22, 2021
• Study Start: April 11, 2021
• Primary Completion: July 2, 2025
• Study Completion: July 2, 2025
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

IL (5); US (9); GB (2); CA (2)