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

NCT04717375 | Terminated Phase 1 Results FDA Drug

• 5 other identifiers: TCD17465BND-22-001U1111-1277-44212023-504937-30-002023
• Study Type: interventional
• Target: 125
• Locations: 4 countries
• Sites: 18

Brief Summary

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

Conditions

Cancer; Neoplasm

Outcome Measures

Primary Outcomes (3)

• Part 1: Sub-Parts 1A, 1B and 1C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  An AE was any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence, that at any dose: resulted in death, was life-threatening, required inpatient hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. A TEAE was any AE that developed, worsened, or became serious during the TE period. TE period was defined as the period from the first study treatment administration to the last study treatment administration + 30 days.

  From first dose of study treatment (Day 1) up to 30 days after last dose of study treatment (considering maximum duration of treatment exposure) i.e., up to approximately Part 1-Sub-Part 1A: 51 weeks, Sub-Part 1B: 126.7 weeks, Sub-Part 1C: 99.3 weeks

• Part 1: Sub-Parts 1A, 1B and 1C: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT=drug-related AEs using NCI CTCAE v5.0.Hematological:Grade (G)4 neutropenia \>=7 days(D),G4 febrile neutropenia,G4 thrombocytopenia,G3 thrombocytopenia with bleeding,G4 anemia;\>=G3/higher non-hematological excluding:increase in liver tests resolved in 7D,diarrhea/associated electrolyte abnormalities \& nausea/vomiting controlled by optimal therapy \& prophylaxis if lasting \<72hours(hr),G3 hyperglycemia in diabetes mellitus/decreased glucose tolerance controlled,=\>G3 hypophosphatemia,hypomagnesemia \& hypocalcemia resolved by treatment in 72 hr,G3 endocrinopathy controlled,G3/G4 elevation of amylase or lipase not associated with pancreatitis,laboratory value out of normal range with no clinical correlate \& resolved with medical management to =\<G1 in 7D,G3 rash resolved to \<=G1,cetuximab-related dermatologic toxicity,transient (\<=24 hr) headache resolved to \<=G1,G3 fatigue \<7D,G3 tumor flare,G3 fever not associated with hemodynamic compromise,G3 infusion reaction returned to G1 in \<6 hr.

  Up to 28 days following the administration of study treatment (Day 1 of Cycle 1, at any dose)

• Part 2: Sub-Part 2A: Stage 1 Cohorts C1 and E1 and Sub-Part 2B: Stage 1 Cohort D1: Objective Response Rate (ORR)

  ORR was defined as the percentage of participants in the population of interest with a best overall response (BOR) of either complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors (RECIST) version (v)1.1. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, i.e., approximately 36 weeks for Cohort C1, 25 weeks for Cohort E1 and 33 weeks for Cohort D1

Secondary Outcomes (22)

• Part 1: Sub-Parts 1A, 1B and 1C: Objective Response Rate

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, i.e., approximately 47 weeks for Sub-Part 1A, 122.7 weeks for Sub-Part 1B and 95.3 weeks for Sub-Part 1C

• Part 1: Sub-Part 1A: Maximum Observed Serum Concentration (Cmax) of SAR444881

  pre-dose, EOI, 4, 8, 24 hours and 7 days post-dose 1 in Cycle 1 Day 1; pre-dose of dose 2 in Cycle 1 Day 15

• Part 1: Sub-Parts 1B and 1C: Maximum Observed Serum Concentration of SAR444881

  Part 1B: pre-dose, EOI, 4, 8, 24 hours and 7 and 14 days post-dose in Cycle 1 Day 1; pre-dose in Cycle 2 Day 1; Part 1C: pre-dose, EOI, 4, 8, 24 hours and 7 days post-dose in Cycle 1 Day 1; pre-dose in Cycle 1 Day 15

• Part 2: Sub-Part 2A: Stage 1 Cohorts C1 and E1, Sub-Part 2B: Stage 1 Cohot D1: Maximum Observed Serum Concentration of SAR444881

  Pre-dose, EOI (1 hour after infusion start), 24 hours and 7 days post dose in Cycle 1 Day 1; pre-dose in Cycle 1 Day 15

• Part 1: Sub-Part 1A: Last Concentration Observed Above the Lower Limit of Quantification (Clast) of SAR444881

  Pre-dose, EOI, 4, 8, 24 hours and 7 days post-dose 1 in Cycle 1 Day 1; pre-dose of dose 2 in Cycle 1 Day 15

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:

• Participants with unresectable or metastatic disease who were refractory to or were not candidates for standard approved therapy
• Histologic confirmation of malignancy
• Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
• Participants must be with 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 participants: acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV); HCC participants: 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

Limitations and Caveats

Study was terminated early due to strategic reasons (not related to safety) and thus randomization was stopped to Part 2: Sub-Part 2A and 2B: Stage 1 (Cohort A1 and B1) and Stage 2 (Cohorts A1 to E1). No participants were enrolled in Part 2 Sub-Part 2A Stage 1 Cohorts A1, B1 and Stage 2 Cohorts A1-E1 as decided by Sponsor (not related to safety). Only results from Part 1: Sub-Parts 1A, 1B and 1C and Part 2: Sub-Parts 2A and 2B Stage 1: Cohorts C1, E1 and D1 are reported.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610 ext: #6

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: September 29, 2026
• Results First Posted: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share

Locations

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