161TiP - A Phase 1/2, Open-label Study of an Anti-ILT2 (LILRB1) Antibody, SAR444881, Administered Alone and in Combination With Pembrolizumab, With or Without Chemotherapy, or Cetuximab in Patients With Advanced Solid Tumors

Background

Immunoglobulin-like transcript-2 (ILT2), also known as LILRB1, an inhibitory receptor expressed on various immune cells, binds to classical and nonclassical major histocompatibility complex class-I (MHC-I), with highest affinity to human leukocyte antigen-G (HLA-G). HLA-G is expressed on various solid tumors and the interaction of ILT2 with HLA-G was found to impair phagocytosis, cytotoxicity, and cytokine secretion of macrophages, natural killer (NK) cells, and T cells. SAR444881 (BND-22), a novel humanized immunoglobulin G4 monoclonal antibody (mAb), selectively binds to ILT2 and blocks its interaction with MHC-I on tumor cells and may restore immune cell functions. (Mandel I, et al. J Immunother Cancer. 2022) In preclinical studies, SAR444881 alone and in combination with an anti-programmed cell death protein-1 mAb demonstrated enhanced anti-tumor activities of macrophages, NK cells, and T cells. (Mandel I, et al. Cancer Res. 2020).

Trial Design

This is a Phase 1/2, open-label, multicenter, dose escalation, optimization, and expansion study evaluating safety, tolerability, and anti-tumor activity of intravenous (IV) SAR444881 as monotherapy and in combination with pembrolizumab, with or without chemotherapy, or cetuximab in patients with advanced solid tumors (NCT04717375). Study has 2 parts: dose escalation (Part 1; n=156) and dose optimization/expansion (Part 2; n=300). Part 1 has three sub-parts - SAR444881 monotherapy (Part 1A; IV, every two weeks [Q2W]), SAR444881 + pembrolizumab (Part 1B; IV, Q3W), and SAR444881 + cetuximab (Part 1C; IV, Q2W). Primary objectives for Part 1 are safety and tolerability and determining the maximum tolerated dose or maximum administered dose of SAR444881 monotherapy or its combinations and for Part 2 are preliminary anti-tumor activity and identification of SAR444881 optimal dose with its combinations. Key secondary objectives include anti-tumor activity, pharmacokinetics, immunogenicity, safety, and tolerability. Study is accruing patients in the United States and Israel. Study opened on March 2021 and has enrolled 71 patients as of August 2023.

Editorial acknowledgement

Medical writing support was provided by Parag Betkar of Sanofi.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

R. Perets: Financial Interests, Personal, Other, Consultant: Galmed Therapeutics, Gilboa Therapeutics, 1E Therapuetics; Financial Interests, Institutional, Local PI: Jannsen, MSD, BMS, Genentech, Amgen, AbbVie, Ammune; Financial Interests, Institutional, Coordinating PI: Biomica; Non-Financial Interests, Institutional, Product Samples, Antibody for research: AbbVie. S.M. Stemmer: Financial Interests, Personal, Research Grant: CAN-FITE, AstraZeneca, BiolineRx, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelixis, Geicam, Incyte, Lilly, Moderna, Teva Pharmaceuticals and Roche; Financial Interests, Personal, Stocks/Shares: CTG Pharma, DocBoxMD, TyrNovo, VYPE, Cytora and CAN-FITE. R. Geva: Financial Interests, Personal, Advisory Board: Medison, Roche, Janssen, MSD, and Pfizer; Financial Interests, Personal, Advisory Role: Eisai, AstraZeneca, Bayer, MSD, BOL Pharma, Ranium, JNJ, and Roche; Financial Interests, Personal, Other, travel and accommodation expenses: Takeda, Pyxis; Financial Interests, Personal, Other, equity interests: BOL Pharma and Pyxis Oncology. T. Golan: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Received honoraria or consultation fees: AbbVie, MSD Merck, Teva; Financial Interests, Personal, Other, Received receipt of speakers bureau: AbbVie. M. Fakih: Financial Interests, Personal, Research Grant: Amgen, AstraZeneca, Novartis; Financial Interests, Personal, Other, Personal Fees: Amgen, AstraZeneca, Novartis; Financial Interests, Personal, Advisory Role: Array, Bayer, GSK, Taiho, Incyte, and Pfizer. J. Cohen: Financial Interests, Personal, Other, Received honoraria: AstraZeneca, Roche, Medison Pharma; Financial Interests, Personal, Advisory Board, Travel and accommodation: Medison Pharma. Z. Jin: Financial Interests, Personal, Other, Consulting or Advisory Role: Novartis, QED Therapeutics, Lilly, GSK, Daichi Sankyo/AstraZeneca. P. Lorusso: Financial Interests, Personal, Advisory Board: AbbVie, Genmab, Genentech, CytomX, Takeda, Cybrexa, Agenus, IQVIA, TRIGR, Pfizer, ImmunoMet, Black Diamond, Astellas, GSK, QED Therapeutics, AstraZeneca, EMD Serono, Shattuck, Salarius, Silverback, MacroGenics, Kyowa Kirin, Kineta, Bayer, Zentalis, Molecular Templates, ABL Bio, STCube, Relay Therapeutics, Stemline, Compass BADX, BAKX Therapeutics, Scenic Biotech, Qualigen, Roivant Sciences, NeuroTrials, Seagen, imCheck, Mekanist, Mersana; Financial Interests, Personal, Other, Data Safety Monitoring Board: Agios, Five Prime, Halozyme; Financial Interests, Personal, Other, imCORE Alliance: Roche-Genentech; Financial Interests, Personal, Other, Consultant: Sotio, SK Life; Financial Interests, Personal, Other, Data Safety Monitoring Committee: Tyme; Financial Interests, Personal, Stocks/Shares: BAXK; Financial Interests, Institutional, Local PI: AbbVie, ADC Therapeutics, Boehringer Ingelheim, ALX Oncology, Astellas Pharma, Astex Pharmaceuticals, AstraZeneca, Bayer, Black Diamond, Calico Life Sciences, Corvus Pharmaceuticals, CytomX Therapeutics, Eisai Pharmaceuticals, Eli Lilly, EMD Sernono, Five Prime, FLX Bio, F-Star Delta Limited, Genentech, MedImmune, Genmab, Incyte, Linnaeus Therapeutics, Merck Sharp & Dohme, Moderna Therapeutics, NextCure, Pfizer, Takeda, Ribon Therapeutics, Sotio, Stemline Therapeutics, Tesaro, Jounce; Financial Interests, Personal, Advisory Board, Advisory Board & Consultant: I-Mab; Non-Financial Interests, Personal, Other, AACR Methods in Clinical Cancer Research Workshop - Co-Director: American Association for Cancer Research; Non-Financial Interests, Personal, Other, AACR Annual Report Committee - Member: American Association for Cancer Research; Non-Financial Interests, Personal, Other, Continuing Medical Education Committee - Member: American Association for Cancer Research; Non-Financial Interests, Personal, Other, Molecular Cancer Therapeutics Editorial Board - Member: American Association for Cancer Research; Non-Financial Interests, Personal, Other, ASCO Conquer Cancer Young Investigator Award Grand Selection Committee - Member: American Society of Clinical Oncology; Non-Financial Interests, Personal, Other, Chair - Phase 0 Task Force: American Association of Cancer Research; Non-Financial Interests, Personal, Other, AACI Clinical Research Innovation Steering Committee - Member: Association of American Cancer Institutes; Non-Financial Interests, Personal, Other, New Drugs in Oncology Seminar Planning Committee - Member: American Society of Clinical Oncology; Non-Financial Interests, Personal, Other, New Agents Committee: Translational Research Panel - Chair: Cancer Research Unite Kingdom; Non-Financial Interests, Personal, Other, Scientific Advisory Board - Member: Targeted Anti-Cancer Therapies; Non-Financial Interests, Personal, Member: American Association for Cancer Research, ASCO; Other, Personal, Other, Investigational Drug Steering Committee - Committee Member: National Cancer Institute; Other, Personal, Other, Phase I Special Emphasis Panel - Grant Reviewer/Discussion Leader: National Cancer Institute; Other, Personal, Other, NeXT Special Emphasis Panel - Grant Reviewer: National Cancer Institute/National Institute of Health; Other, Personal, Other, Board of Scientific Counselors, Clinical Sciences & Epidemiology: National Cancer Institute; Other, Personal, Other, Young Investigator Meeting, Cancer Therapy Evaluation Program - Professor: National Cancer Institute; Other, Personal, Other, Academic Advisory Board SPORE GI Malignancies - Case Western Reserve University: Case Western Reserve University; Other, Personal, Other, Scientific External Advisory Board - Member: University of California at San Diego; Other, Personal, Other, External Advisory Board - Member: University of Arizona; Other, Personal, Other, External Scientific Advisory Board - Member: University of New Mexico. N. Ashtamker, I. Friedman, M. Hakim: Financial Interests, Personal, Other, Employed by Biond Biologics: Biond Biologics; Financial Interests, Personal, Stocks/Shares: Biond Biologics. N. Crawford, R. Perez, M. Agarwal, G. Abbadessa, J. Lin, C. Deantonio: Financial Interests, Personal, Other, Employed by Sanofi: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. Financial Interests, Personal, Stocks/Shares: Sanofi. M. Wu: Financial Interests, Personal, Other, Employed by Sanofi: Sanofi; Financial Interests, Personal, Stocks or ownership: Sanofi. M. Borad: Financial Interests, Institutional, Other, Received grant to institution: Senhwa Pharmaceuticals, Adaptimmune, Agios Pharmaceuticals, Halozyme Pharmaceuticals, Five Prime Pharmaceuticals, Celgene Pharmaceuticals, EMD Merck Serono, Toray, Dicerna, Taiho Pharmaceuticals, Sun Biopharma, Isis Pharmaceuticals, Redhill Pharmaceutical; Financial Interests, Personal, Other, travel support: AstraZeneca. All other authors have declared no conflicts of interest.