Abstract 983P
Background
BI 765063 is a first-in-class, humanised IgG4 monoclonal antibody antagonist of SIRPα (expressed on myeloid cells) that blocks the “don't eat me” signal of the SIRPα/CD47 axis, a critical innate immune checkpoint, enhancing tumour cell phagocytosis and increasing antigen presentation to drive anti-tumour responses. This dose escalation/expansion study aimed to evaluate the safety and efficacy of BI 765063 as monotherapy, then with ezabenlimab (PD-1 inhibitor) in pts with advanced solid tumours. BI 765063 monotherapy was well tolerated and demonstrated activity, including a PR in a pt with hepatocellular carcinoma. Here we report preliminary results of the combination.
Methods
Step 1 (escalation) enrolled pts who were genetically SIRPα V1/V1 homozygous or V1/V2 heterozygous with advanced solid tumours who failed/were not eligible for standard therapy. Two BI 765063 dose levels (18 and 24 mg/kg IV q3w) were evaluated with ezabenlimab (240 mg IV q3w). A Bayesian Logistic Regression Model with overdose control was used. Primary endpoints included dose-limiting toxicities (DLTs) in Cycle 1 and the maximum tolerated dose (MTD). Other endpoints included AEs and efficacy (ORR: RECIST 1.1).
Results
As of April 2021, 12 pts (6 V1/V1, 6 V1/V2) have received ≥1 dose of each therapy. Pt tumour types were GI (n=5), gynaecological (n=5), NSCLC and melanoma (n=1 each). No DLTs were reported; the MTD was not reached. The only treatment-related AE observed in >1 pt was grade 1/2 infusion-related reaction (n=3). No treatment-related anaemia or thrombocytopenia was observed. A pt with colonic adenocarcinoma (V1/V1, Micro Satellite Stable [MSS]), had tumour shrinkage (-27%) 12 weeks from therapy start. A pt with endometrial carcinoma (V1/V2, MSS) had a confirmed PR (-37%) maintained 12 weeks from therapy start. Both pts were PD-1 treatment-naïve.
Conclusions
The first-in-class, selective SIRPα inhibitor BI 765063 + ezabenlimab had a good safety profile in the first 12 pts. One pt had a confirmed PR. The escalation in combination (n=18) will conclude in June 2021; updated data will be presented.
Clinical trial identification
NCT03990233.
Editorial acknowledgement
Medical writing support for the development of this abstract, under the direction of the authors, was provided by Steven Kirkham, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by Boehringer Ingelheim.
Legal entity responsible for the study
OSE Immunotherapeutics with the support of Boehringer Ingelheim.
Funding
OSE Immunotherapeutics with the support of Boehringer Ingelheim.
Disclosure
N. Kotecki: Financial Interests, Institutional, Principal Investigator: OSE immunotherapeutics; Non-Financial Interests, Personal, Principal Investigator: OSE immunotherapeutics. S. Champiat: Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Oncovita; Financial Interests, Personal, Other, Travel and congress: AstraZeneca; Financial Interests, Personal, Other, Travel and congress: MSD; Financial Interests, Personal, Other, Travel and congress: Roche; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Abbvie; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Adaptimmune; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Aduro Biotech; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Agios Pharmaceuticals; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Amgen; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Argen-X Bvba; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Arno Therapeutics; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Astex Pharmaceuticals; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: AstraZeneca Ab; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Aveo; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Basilea Pharmaceutica International Ltd; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Bayer Healthcare Ag; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Bbb Technologies Bv; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Beigene; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Blueprint Medicines; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Boston Pharmaceuticals; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Ca; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Celgene Corporation; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Chugai Pharmaceutical Co; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Clovis Oncology; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Cullinan-Apollo; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Debiopharm; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Eisai; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Eisai Limited; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Eli Lilly; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Exelixis; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Faron Pharmaceuticals Ltd; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Forma Tharapeutic; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Gamamabs; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Genentech; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: GlaxoSmithKline; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: H3 Biomedicine; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Hoffmann La Roche Ag; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: ImCheck Therapeutics; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Innate Pharma; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Institut De Recherche Pierre Fabre; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Iris Servier; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Janssen Cilag; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Janssen Research Foundation; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Kura Oncology; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Kyowa Kirin Pharm. Dev; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Lilly France; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Loxo Oncology; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Lytix Biopharma As; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Medimmune; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Menarini Ricerche; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Merck Sharp & Dohme; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Merrimack Pharmaceuticals; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Merus; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Millennium Pharmaceuticals; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Molecular Partners Ag; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Nanobiotix; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Nektar Therapeutics; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Novartis Pharma; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Octimet Oncology Nv; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Oncoethix; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Oncopeptides; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Orion Pharma; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Ose Pharma; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Pfizer; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Pharma Mar; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Pierre Fabre; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Medicament; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Roche; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Sanofi Aventis; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Seattle Genetics; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Sotio A.S; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Syros Pharmaceuticals; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Taiho Pharma; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Tesaro; Financial Interests, Institutional, Principal Investigator, Principal/sub-Investigator of Clinical Trials: Xencor; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP), Research Grants: AstraZeneca; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP), Research Grants: BMS; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP), Research Grants: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP), Research Grants: Janssen Cilag; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP), Research Grants: Merck; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP), Research Grants: Novartis; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP), Research Grants: Onxeo; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP), Research Grants: Pfizer; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP), Research Grants: Roche; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP), Research Grants: Sanofi; Non-Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): AstraZeneca; Non-Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): Bayer; Non-Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): BMS; Non-Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): Boringher Ingelheim; Non-Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): Medimmune; Non-Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): Merck; Non-Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): NH TherAGuiX; Non-Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): Onxeo; Non-Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): Pfizer; Non-Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP), Non-financial support (drug supplied): Roche. J. Delord: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Roche/Genentech; Financial Interests, Institutional, Advisory Role: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Role: MSD Oncology; Financial Interests, Institutional, Other, Research Funding: Genentech; Financial Interests, Institutional, Other, Research Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Research funding: MSD Oncology; Financial Interests, Institutional, Other, Research Funding: AstraZeneca; Financial Interests, Institutional, Other, Research Funding: Transgene. A. Marabelle: Financial Interests, Personal, Principal Investigator, Principal Investigator of Clinical Trials from the following companies: Roche/Genentech, BMS, Merck (MSD), Pfizer, Lytix pharma, Eisai, AstraZeneca/Medimmune, Tesaro, Chugai, OSE Immunotherapeutics, SOTIO, Molecular Partners, ImCheck, Pierre Fabre, Adlai Nortye; Financial Interests, Personal, Principal Investigator, Principal Investigator of the following academic trials: ACSE NIVOLUMAB/NCT03012581 (funding: INCa, Ligue contre le Cancer & BMS; drug supply: BMS, Ligue contre le Cancer & BMS; sponsor Unicancer), ISI-JX/NCT02977156 (funding & drug supply: Transgene; sponsor Leon Berard Cancer Center), NIVIPIT/NCT02857569; Financial Interests, Personal, Member, Member of Clinical Trial Steering Committee: NCT02528357: GSK; Financial Interests, Personal, Member, Member of Clinical Trial Steering Committee: NCT03334617: AstraZeneca; Financial Interests, Personal, Member, Member of Data Safety and Monitoring Board: NCT02423863 (Sponsor: Oncovir): Oncovir; Financial Interests, Personal, Member, Member of Data Safety and Monitoring Board: NCT03818685 (Sponsor: Centre Léon Bérard): Centre Léon Bérard; Financial Interests, Personal, Advisory Board, Scientific Advisory Boards: Merck Serono, eTheRNA, Lytix pharma, Kyowa Kirin Pharma, Novartis, BMS, Symphogen, Genmab, Amgen, Biothera, Nektar, Tesaro/GSK, Oncosec, Pfizer, Seattle Genetics, AstraZeneca/Medimmune, Servier, Gritstone, Molecular Partners, Bayer, Partner Therapeutics; Financial Interests, Personal, Other, Teaching/Speaker activities: Roche/Genentech, BMS, Merck (MSD), Merck Serono, AstraZeneca/Medimmune, Amgen, Sanofi, Servier; Financial Interests, Personal, Other, Scientific & Medical Consulting: Roche, Pierre Fabre, Onxeo, EISAI, Bayer, Genticel, Rigontec, Daichii Sankyo, Imaxio, Sanofi/BioNTech, Molecular Partners, Pillar Partners, BPI, Faron, Applied Materials; Non-Financial Interests, Personal, Other, Non-Financial Support (travel expenses): AstraZeneca, BMS, Merck (MSD), Roche; Financial Interests, Personal, Stocks/Shares, Shareholder: Pegascy SAS, Centessa Pharmaceuticals, HiFiBio, Shattuck Labs; Financial Interests, Personal, Other, Patent holder: Patent Issued (not licensed): “Humanized and Chimeric Monoclonal Antibodies to CD81”, Stanford Office of Technology Licensing, 3000 El Camino Real, Bldg. 5, Suite 300, Palo Alto, CA 94306-2100. U.S. Application Serial No. 62/351,054: Stanford Office of Technology Licensing; Financial Interests, Institutional, Research Grant, Pre-Clinical and Clinical Research Grants (Institutional Funding): Merus, BMS, Boehringer Ingelheim, Transgene, Fondation MSD Avenir, Sanofi; Financial Interests, Personal, Member, Member of the following scholar societies: European Society for Medical Oncology (ESMO), American Society for Clinical Oncology (ASCO), American Association for Cancer Research (AACR), European Academy for Tumor Immunology (EATI). Founder and president of the French society for Immunotherapy of Ca; Financial Interests, Personal, Member, Supervisory Board Member: Gustave Roussy Foundation; Financial Interests, Personal, Member, Member of the Steering Committee of the Immuno-Oncology Task Force at Unicancer. Member of the Editorial Boards of the European Journal of Cancer and ESMO IO Tech: Immuno-Oncology Task Force at Unicancer. Member of the Editorial Boards of the European Journal of Cancer and ESMO IO Tech; Financial Interests, Institutional, Other, Sub-Investigator of Clinical Trials sponsored by the following companies: 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 Medicine; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Non-financial support (drug supply to Gustave Roussy sponsored trials): AstraZeneca, Bayer, BMS, Boringher Ingelheim, Medimmune, MSD, NH TherAGuiX, Pfizer, Roche. S. Wojciekowski: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim Pharma GmbH & Co KG. E. Block: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim Pharmaceuticals, Inc. N. Clarke: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim Pharma GmBH & Co. KG. C. Fromond: Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeurics. N. Poirier: Financial Interests, Personal, Member of the Board of Directors: OSE Immunotherapeutics; Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics; Financial Interests, Personal, Stocks/Shares: OSE Immunotherapeutics. D. Costantini: Financial Interests, Personal, Member of the Board of Directors: OSE Immunotherapeutics; Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics; Financial Interests, Personal, Stocks/Shares: OSE Immunotherapeutics. B. Vasseur: Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics; Financial Interests, Personal, Stocks/Shares: OSE Immunotherapeutics. P.A. Cassier: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Principal Investigator: AbbVie; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Blueprint; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Exelixis; Financial Interests, Institutional, Principal Investigator: Janssen; Financial Interests, Institutional, Principal Investigator: Eli Lilly; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Roche/Genentech; Financial Interests, Institutional, Principal Investigator: Taiho; Financial Interests, Institutional, Principal Investigator: Transgene; Financial Interests, Institutional, Principal Investigator: Toray. All other authors have declared no conflicts of interest.