Abstract 704TiP
Background
SAR445256 (KY1044) is a fully human IgG1 targeting ICOS with a dual mechanism of action: dose dependent depletion of ICOShigh Tregs in tumor microenvironment and activation of ICOSlow Teff. NCT03829501 is the first in human study testing safety, efficacy, and pharmacological properties of SAR445256 with/without atezolizumab in PD-L1 naïve or pretreated pts with advanced malignancies. Dose escalation part was guided by an adaptive dose-finding method and Ph 1 enrichment part was included for a better understanding of safety, tolerability, preliminary anti-tumor efficacy and PK/PD relationships of SAR445256 in combination with atezolizumab. Selected Ph2 dose was 8mg with atezolizumab 1200mg, both given IV, Q3W. In Ph1, a 59-year-old male pt with HPV+ HNSCC who progressed on 5 prior lines of therapy (including nivolumab), experienced a PR (42% tumor shrinkage), still holding as of C26D1, and on treatment for >20 months as of 10Feb2022. Strong expression of ICOS on intratumoral Tregs in head and neck cancer as well as the promising clinical activity previously reported suggest HNSCC to be favorable indication for SAR445256.
Trial design
Ph2 cohorts (2 cohorts, PD-L1 naïve and pretreated) are being initiated in HNSCC pts. Approximately 40 pts will be enrolled in each cohort. Key inclusion criteria: anti -PD-L1 therapy naïve and pretreated, 1-2 prior lines of systemic therapy for advanced disease, histologically documented advanced/metastatic malignancies, measurable disease by RECIST 1.1, site of disease amenable to biopsy. Key exclusion criteria: CNS metastases, active autoimmune disease, significant heart disease and/or QT prolongation, steroid therapy, or any immunosuppressive therapy. Efficacy measures will be performed as per RECIST 1.1 Q8W for the first 16 weeks and then Q12W, while AEs will be classified according to CTCAE v5. SAR445256 was well tolerated and showed initial signs of activity, in a HNSCC pt who received multiple prior lines of therapy. Ph2 assessment is planned in 2 cohorts: HNSCC pts PD-L1 naïve and pretreated. Note: Atezolizumab will continue to be provided by Roche for the RP2D part of this study as well. 1. Sainson R et al 2020. 2. Patel MR et al 2021.
Clinical trial identification
NCT03829501.
Editorial acknowledgement
Mukul Rastogi, PhD of Sanofi.
Legal entity responsible for the study
Sanofi.
Funding
Sanofi.
Disclosure
M. Patel: Financial Interests, Personal, Speaker’s Bureau: Exelis, Genentech/Roche, Taiho Pharmaceutical, Celgene/BMS; Financial Interests, Personal, Advisory Board: Mirati, Daiichi; Non-Financial Interests, Institutional, Funding: Acerta Pharma, ADC Therpeutics, Agenus Aileron Therapeutic, AstraZeneca, Bicycle Therapeutics, BioNTech AG, Boehringer Ingelheim, Calithera Biosciences, Celgene Checkpoint Therapeutics CicloMed, Clovs Oncology, Curis Cyteir, Daiichi Sankyo, eFFECTOR ; Financial Interests, Personal, Advisory Role: Pharmacyclics/Janssen, Pfizer/EMD Serono; Financial Interests, Personal, Other, Travel, accommodation, expenses, honoraria: Pfizer, Pharmacyclics, Bayer, Janssen Oncology, Genentech. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: 4SC, AstraZeneca, BMS, Boehringer Ingelheim, Idera, Immunocore, Merck Serono, MSD, Nektar, Novartis, Pfizer/Array, Pierre fabre, Regeneron, Roche Genentech, Sandoz, Sanofi, Sun Pharma; Financial Interests, Personal, Other, Consultant Role: Bio-I Health, Daiichi Sankyo, Italfarmaco, Lunaphore, Medicenna, Nouscom, Oncosec, Pfizer; Financial Interests, Institutional, Funding, Clinical Trial: BMS, Pfizer,/Array, Roche Genentech, Sanofi; Non-Financial Interests, Personal, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Personal, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Personal, Leadership Role, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Personal, Member, Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Personal, Member: AIOM, ASCO, EORTC Melanoma Cooperative Group, SITC, SMR; Financial Interests, Personal, Other, Travel: MSD. F. Thistlethwaite: Financial Interests, Personal, Advisory Board, honoraria: Bayer; Financial Interests, Personal, Advisory Board, Ad board: BMS, Zelluna; Financial Interests, Personal, Advisory Board, Ad boards: GSK; Financial Interests, Personal, Advisory Board, Adboard/consultancy: Tknife; Financial Interests, Personal, Advisory Board: Adicet, Janssen, EnaraBio, Immatics, Ixaka; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Other, iMATCH is a 12 partner consortium funded by not for profit Innovate UK (UK government body) partners include commercial, clinical and academic institutes. I am director and my salary (0.2WTE) is supported through this work as a grant to my institution (The Christie NHS foundation trust - not for profit NHS Hospital) from IUK: iMATCH director; Financial Interests, Institutional, Officer, Clinical lead for this 10 partner consortium of clinical academic and commercial partners. My salary is partly supported (approx. 0.05WTE) through this by a grant paid by Innovate UK (a NFP government body) to my institution (The Christie NHS foundation trust a NFP UK Hospital): Sample; Financial Interests, Institutional, Invited Speaker: Pfizer, GenMab, Synthon, CytomX, Incyte, Janssen, Adaptimmune, Aveo, BMS, GSK, Roche, AbbVie, Immunocore, Achilles ltd, Agalimmune Ltd, Kymab Ltd, Chugai, Millenium Pharmaceuticals/Takeda, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Other, Panel member for a funding committee (MRC is a UK government NFP organisation): MRC DPFS panel member. D.R. Adkins: Financial Interests, Personal, Advisory Role: Merck, Cue Biopharma, Blueprint Medicine, Exelixis, Immunitas, Kura Oncology, Tagimmune Therapeutics, Twoxar, Vaccinex, Xilio Therapeutics, Boehringer Ingelheim ; Financial Interests, Institutional, Principal Investigator: Kymab, Pfizer, Eli Lilly, Merck, Celgene, Novartis, AstraZeneca, Blueprint Medicine, Kura Oncology, Exelixis, Matrix Biomed, Aduro Biotech, Cue Buipharam, Cofavtor genomics, Shanghai Denovo, Hookipa, Debio, Adlai Nortye, BeiGene, Conjupro, Epizyme, Gilea. V. Meucci Villaflor: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson; Financial Interests, Institutional, Principal Investigator: Takeda. D. Galizia: Financial Interests, Personal, Other, Public Speaking: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: MSD. L. Calabro: Financial Interests, Personal, Invited Speaker: BMS, MSD, Roche, Sanofi; Non-Financial Interests, Advisory Board: BMS, MSD; Non-Financial Interests, Other, Educational Activity: Sanofi, Roche. M. Di Maio: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator: BeiGene, Exelixis, MSD, Pfizer, Roche; Financial Interests, Institutional, Research Grant: Tesaro-GSK. C. Deantonio: Financial Interests, Personal, Full or part-time Employment, May also hold share/stock options: Sanofi. Y. Yang: Financial Interests, Personal, Full or part-time Employment, May also hold share/stock options: Sanofi. D. Kurup: Financial Interests, Personal, Full or part-time Employment, May also hold share/stock options: Sanofi. G. Abbadessa: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. All other authors have declared no conflicts of interest.