Abstract 30P
Background
Anti-PD-1 antibodies have shown significant clinical efficacy with manageable safety. OSE279 is a humanized S228P- IgG4 monoclonal bivalent antibody against PD-1 which will be further used as the anti-PD-1 backbone component of a bifunctional checkpoint inhibitor BiCKI ® platform.
Methods
A FIH study investigating OSE279 is ongoing, evaluating 2 Dose Levels (DLs) of 100 and 300 mg given q3w and 1 DL of 600 mg q6w, according to BOIN design, in subjects with advanced malignancies who progressed on standard treatments, and for which anti-PD1/PDL1 have shown efficacy but are not locally available. Primary objective is to determine the MTD and/or Recommended Phase 2 Doses (RP2Ds). Secondary objectives are efficacy, safety, PK and PD profiles. Dose-Limiting Toxicity (DLT) period is 21 days. 300 mg was declared RP2D for a q3w regimen, with a DLT of gr3 hepatitis in 1/7 patients, as previously reported. We now report the selection of a second RP2D of 600 mg q6w with an update on safety and preliminary efficacy.
Results
In this FIH study as of November 2023, 19 subjects were treated, with 12 tumor types, the most frequent being Soft Tissue Sarcoma (n=4) and anal Squamous Cell Carcinoma (SCC n=3). Median age was 61y (range 34-77), 10/19 patients (52.6%) were female, median number of prior metastatic lines was 2 (range 1-6). At 600 mg q6w no DLTs were reported in 10 patients. Treatment-Related Adverse Events (TRAEs) occurred in 14/19 patients (73.7%). Serious TRAEs of pneumonitis gr2 and hepatitis gr3 (both at 300mg q3w), and creatinine increased gr2 (at 600 mg/q6w) occurred in 3/19 patients (15.8%). 3 confirmed PR were observed in patients with HCC (300mg/q3w), Undifferentiated Pleomorphic Sarcoma and anal SCC (both 600 mg/q6w). SD was reported in 8 patients. Treatment is ongoing in 9 patients. PK showed dose-proportionality and favorable exposure; sustained RO was observed.
Conclusions
In this FIH study, OSE279 showed a favorable safety profile with signs of efficacy in the first 19 patients treated. 600 mg q6w has been selected as second RP2D. PK and PD profiles were according to modelling. New cohorts testing combinations, including with cancer vaccine, are planned.
Clinical trial identification
NCT05751798; Date first submitted: 2023-01-30.
Editorial acknowledgement
Legal entity responsible for the study
OSE Immunotherapeutics.
Funding
OSE Immunotherapeutics.
Disclosure
M. Robert: Financial Interests, Institutional, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Other, travel and congress fees: AstraZeneca; Non-Financial Interests, Personal, Training: Novartis. C.A. Gomez-Roca: Financial Interests, Personal, Invited Speaker: BMS, Roche / Genentech, Pierre Fabre, BMS, Genentech; Financial Interests, Personal, Other, IDMC member: PharmaMar; Financial Interests, Personal, Advisory Board: Macomics; Financial Interests, Institutional, Research Grant: Roche / Genentech; Financial Interests, Institutional, Invited Speaker: BMS, Amunix, Hookipa, Kazia Therapeutics, Ideaya; Non-Financial Interests, Personal, Member of Board of Directors: FITC (Société française d'Immuno-Thérapies du Cancer); Non-Financial Interests, Personal, Officer: ESMO Membership Committee, ESMO - MCBS Extended Working Group; Non-Financial Interests, Personal, Officer, Young Investigators Committee at imCORE: inFLAME; Non-Financial Interests, Personal, Member of Board of Directors, Network of Early Phase Units: OncoDistinct; Non-Financial Interests, Personal, Leadership Role: FITC (Société française d'Immuno-Thérapies du Cancer). C.P. Massard: Other, Personal, Other: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, BeiGene, Blueprint, BMS, Boehringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 Biomedicine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, PharmaMar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor: Company. S. Postel-Vinay: Financial Interests, Institutional, Advisory Board, Steering Committee: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, As part of the Drug Development Department (DITEP) SPV is Principal/sub-Investigator of Clinical Trials for AbbVie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd., Bayer Healthcare Ag, BBB Technologies BV, Beigene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd., Forma Therapeutics, GamaMabs, Genentech, GSK, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus: Various drug companies; Financial Interests, Institutional, Research Grant, Translational research Funding: IMCore Hoffman LaRoche; Financial Interests, Institutional, Research Grant, preclinical research Funding: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, Principal investigator of phase I/II clinical trials: AstraZeneca, GSK, PEP Therapy, BMS, Novartis; Amgen, Oxford Biotherapeutics, Clovis, Roche. C. Chevalier, L. Cordonnier, A. Morello, M. Déramé, S. Comis, N. Poirier: Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics. C. Josse: Financial Interests, Personal, Full or part-time Employment: Exystat. P. Cassier: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Roche, Amgen, Boehringer Ingelheim; Financial Interests, Personal, Other, Advisor: OSE immunotherapeutics; Financial Interests, Institutional, Invited Speaker: AbbVie, Amgen, Blueprint, Boehringer Ingelheim, Bristol Meyer Squibb, Exelixis, GSK, Incyte, Janssen, Loxo/Eli Lilly, Novartis, Roche, Taiho, Toray Industries, Transgene; Non-Financial Interests, Institutional, Product Samples: Plexxikon, Novartis, MSD, AstraZeneca, GSK. All other authors have declared no conflicts of interest.