1074TiP - A phase I/II, open label, first-in-human, dose escalation and expansion study of SAR445877 administered as monotherapy in adults with advanced solid tumors

Background

SAR445877 (SAR’877) is a fusion protein of high affinity anti-programmed cell death protein 1 (PD1) antibody combined with a detuned interleukin 15 (IL15) (complexed with IL15 receptor sushi domain). SAR’877, via its anti-PD1 moiety, binds to PD-1-expressing T and natural killer (NK) cells and potentially allows for a targeted expansion and activation of CD8+ T and NK cells expressing both PD1 and IL2/15Rβγ. Nonclinical studies have demonstrated SAR’877 as an immune-modulatory agent.¹

Trial design

This is a first in human, open-label, multicenter, dose escalation and expansion phase 1/2 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activities of SAR’877 administered intravenously as a single agent in adult participants with advanced unresectable or metastatic solid tumors (EudraCT 2022-001239-95/NCT05584670). The study is conducted in 2 parts. The Part 1 (dose escalation) will determine the maximum tolerated dose or maximum administered dose per occurrence of dose limiting toxicities in the first 28-days (cycle 1 and 2), recommended dose(s), and the overall safety and tolerability profile of SAR’877. A multicohort Part 2 (dose expansion) would assess the safety and preliminary efficacy of SAR’877 (2 dose levels in at least 1 indication, as applicable) and will include cohorts with advanced solid tumors regardless of the tumor proportion score/combined positive score and cohort with a negative expression of the PDL1. Approximately, 240 participants will be enrolled of which nearly 75 participants will be enrolled in the Part 1 (dose escalation) and 165 participants in the Part 2 (dose expansion). Adverse effects will be assessed per National Cancer Institute, Common Terminology Criteria for Adverse Events version 5.0 and American Society for Transplantation and Cellular Therapy consensus grading. Tumor response will be determined according to Response Evaluation Criteria in Solid Tumors criteria. Dose escalation Part 1 is conducted in US, Spain and Netherlands. The study is enrolling participants. Lu D et al, J Immunother Cancer (2020);8(Suppl 3):573.

Clinical trial identification

EudraCT 2022-001239-95, NCT05584670.

Editorial acknowledgement

Deepshikha Khurana of Sanofi Global Hub.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

M. Gutierrez: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Merck and Lilly; Financial Interests, Personal, Other, Travel, accommodations, expenses: Guardant Health; Financial Interests, Personal, Stocks/Shares: Cota Healthcare; Financial Interests, Personal, Ownership Interest: Cota Healthcare; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Merck, Incyte, NextCure, Pfizer, Roche/Genentech, Boehringer Ingelheim, GSB Pharma, Moderna Therapeutics, Eisai, Silenseed, Regeneron, Sanofi, Johnson & Johnson, MedImmune, Checkpoint Therapeutics, Acerta Pharma, Arcus Biosciences, A. E. Garralda: Financial Interests, Personal, Advisory Role: Roche, Ellipses Pharma, NeoMed, Janssen, Boehringer Ingelheim, Alkermes, Thermo Fisher Scientific, Bristol Myers Squibb, MAB Discovery, Anaveon, F-Star, Hengrui Therapeutics and Sanofi; Financial Interests, Personal, Speaker’s Bureau: MSD, Roche, Thermo Fisher Scientific, Lilly and Novartis; Financial Interests, Personal, Other: Affimed Therapeutics, Amgen, Anaveon, AstraZeneca, BioNTech, Catalym, CytomX Therapeutics, F. Hoffmann LaRoche, F-Star, Genentech, Genmab, Hutchison MediPharma, Imcheck Therapeutics, Immunocore, Janssen-Cilag, MedImmune, Merck KGaA, Novartis, Peptomyc, Ri; Financial Interests, Personal, Research Grant: Novartis, Roche, Thermo Fisher Scientific, AstraZeneca/MedImmune, Taiho Oncology and BeiGene. E. Calvo: Financial Interests, Personal, Full or part-time Employment: START Madrid-CIOCC; Financial Interests, Personal, Advisory Role: Nanobiotix, Janssen-Cilag, Roche/Genentech, TargImmune Therapeutics, Servier, Bristol Myers Squibb, Amunix, Adcendo, Anaveon, AstraZeneca/MedImmune, Chugai Pharma, MonTa Biosciences, MSD Oncology, Nouscom, Novartis, OncoDNA, T-Knife, Elevation Oncology, P; Financial Interests, Personal, Leadership Role: START, PharmaMar, European Organisation for Research and Treatment of Cancer (EORTC), Sanofi, BeiGene, Novartis and Merus NV; Financial Interests, Personal, Other: Investigational Therapeutics in Oncological Sciences, Non for profit Foundation PharmaMar and CRIS Cancer Foundation; Financial Interests, Personal, Stocks/Shares: START and Oncoart Associated; Financial Interests, Personal, Ownership Interest: START and Oncoart Associated; Financial Interests, Personal, Other, honoraria: HM Hospitales; Financial Interests, Personal, Research Grant: START. M. van Dongen: Financial Interests, Personal, Advisory Role: Relay Therapeutics, Merck Sharp & Dohme. F.A. Eskens: Financial Interests, Personal, Invited Speaker, Honoraria: Servier and AstraZeneca; Financial Interests, Personal, Advisory Role: Merck Serono, Roche and Eisai ; Financial Interests, Personal, Invited Speaker, travel, accommodation, expenses: Pfizer. F. Menas: Financial Interests, Personal, Stocks or ownership: Sanofi. C. Zhu: Financial Interests, Personal, Stocks or ownership: Sanofi. M. Wu: Financial Interests, Personal, Stocks or ownership: Sanofi. H. GUILLEMIN-PAVEAU: Financial Interests, Personal, Stocks or ownership: Sanofi. G. Abbadessa: Financial Interests, Personal, Stocks or ownership: Sanofi. R. Perez: Financial Interests, Personal, Stocks or ownership: Sanofi. O. Yildirim: Financial Interests, Personal, Stocks or ownership: Sanofi. A. Naing: Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Personal, Advisory Role: CytomX Therapeutics, OncoSec, STCube Pharmaceuticals Inc, Genome & Company, Deka Biosciences, NGM Biopharmaceuticals, PsiOxus Therapeutics, Immune-Onc Therapeutics, Nouscom, Merck Sharp & Dohme, OncoNano Inc, Servier, Lynx Health, AbbVie; Financial Interests, Personal, Other, Travel and Accommodation: ARMO BioSciences, NeoImmuneTech, NGM Biopharmaceuticals; Financial Interests, Personal, Other, Honoraria: AKH Inc, Lynx Group, Society for Immunotherapy of Cancer, Korean Society of Medical Oncology Scripps Hospital, American Society of Clinical Oncology, ESMO and CME Outfitters; Financial Interests, Personal and Institutional, Research Funding: National Cancer Institute, EMD Serono, MedImmune, Atterocor, Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance BioSciences Inc, Healios, Kymab, PsiOxus Therapeutics, Arcus Biosciences, NeoImmuneTech, ImmuneOncia, Surface Oncology, Monopteros Therapeutics, BioNTech SE, Seven and Eight Biopharmaceuticals, Sotio, Lilly. All other authors have declared no conflicts of interest.