697P - Open-label, phase I, dose escalation/expansion trial of the anti-SIRPα monoclonal antibody BI 770371 in patients with advanced solid tumours, alone or in combination with the anti-PD-1 monoclonal antibody ezabenlimab

Background

BI 770371, a pan-specific anti-signal regulatory protein alpha (SIRPα) monoclonal antibody (mAb), reactivates innate and adaptive anti-tumour immune responses. This phase I, non-randomised, open-label, multicentre trial (NCT05327946) aimed to determine the maximum-tolerated dose (MTD) and recommended dose for expansion of BI 770371 ± ezabenlimab.

Methods

BI 770371 was administered alone or in combination with ezabenlimab IV once every 3 weeks in patients with advanced solid tumours. Treatment continued until progressive disease, unacceptable toxicity or other withdrawal criteria. Dose escalation was guided by a Bayesian Logistic Regression Model with overdose control. Primary endpoint was dose-limiting toxicities (DLTs) in the MTD evaluation period. Secondary endpoints were adverse events (AEs) and DLTs in the on-treatment period.

Results

As of 31 March 2023, 18 patients (monotherapy, n=15; combination therapy, n=3) have been treated in Canada, Japan and the US. In the patients who received monotherapy, the most common tumour types were colorectal, ovarian and prostate cancer (n=2 patients with each). 53% of patients were male, 53% had ECOG PS 0 and all had received >2 prior lines of treatment. AEs were reported in 12 patients (80%) and grade 3 AEs were reported in one patient (peripheral oedema, atrial fibrillation). Treatment-related AEs were observed in 10 patients (67%; all grade 1/2); the most common were pruritus (n=5) and peripheral oedema (n=2). Serious AEs were reported in four patients (27%; atrial fibrillation, decreased appetite, encephalitis, hypoxia, disease progression). Only one patient had an AE leading to treatment discontinuation (encephalitis). In 14 evaluable patients, 11 (73%) achieved a best response of stable disease. In the MTD evaluable set (n=15 monotherapy, n=3 combination therapy), no DLTs were reported during the MTD evaluation period. The MTD has not been reached; dose escalation is ongoing.

Conclusions

BI 770371 showed manageable toxicity alone and in combination with ezabenlimab. The trial is ongoing.

Clinical trial identification

NCT05327946.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Frans Everson, of Ashfield MedComms, an Inizio Company, and funded by Boehringer Ingelheim

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

M. Gutierrez: Financial Interests, Personal, Advisory Board: Sanofi, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Guardant; Financial Interests, Personal, Other, Consulting: Celularity, Merck. R. Jamal: Financial Interests, Personal, Advisory Board: BMS, Medison Pharma; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, Bristol Myers Squibb, Iovance Biotherapeutics; Financial Interests, Institutional, Principal Investigator: Princiapal Investigaor in multiple industry led trial. N. Yamamoto: Financial Interests, Personal, Invited Speaker: ONO, Chugai, Daiichi Sankyo, Eisai; Financial Interests, Personal, Advisory Board: Eisai, Takeda, Boehringer Ingelheim, Cimic, Chugai, Healios; Financial Interests, Institutional, Local PI, Principal Investigator in industry sponsored trial: Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, ONO, Janssen Pharma, MSD, Merck, GSK, Sumitomo Dainippon, Chiome Bioscience, Otsuka; Financial Interests, Institutional, Local PI, Principal investigator in industry sponsored trial: Carna Biosciences, Genmab, Shionogi, TORAY; Financial Interests, Institutional, Research Grant, Principal investigator in industry sponsored trial: Rakuten Medical, InventisBio Co., Ltd. T. Doi: Financial Interests, Personal, Other, Advisory Role: Noile-Immune Biotech, Oncolys BioPharma, Boehringer Ingelheim, A2 Healthcare, Nano Carrier, PRA Health Sciences, Kaken Pharma, Chugai Pharma, Sumitomo Pharma, Shionogi, Otsuka Pharma, Takeda, Kyowa Kirin, Rakuten Medical, Giliad; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Taiho, MSD, AbbVie, Eisai, Pfizer, BMS, Janssen Pharma, Daiichi Sankyo, Chugai Pharma, Boehringer Ingelheim, PRA Health Sciences, Amgen, GSK, Shionogi, RIN Institute, ONO Pharma. M. Elgadi: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J.L. Ferrada: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. S.M. Wojciekowski: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. M.R. Patel: Financial Interests, Personal, Leadership Role: ION Pharma; Financial Interests, Personal, Other, Honoraria: Janssen Oncology; Financial Interests, Personal, Speaker, Consultant, Advisor: Olema Pharmaceuticals; Financial Interests, Institutional, Research Funding: Acerta Pharma, ADC Therapeutics, Agenus, Aileron Therapeutics, AstraZeneca, BioNTech AG, Boehringer Ingelheim, Celgene, CicloMed, Clovis Oncology, Cyteir Therapeutics, Daiichi Sankyo, Lilly, Evelo Therapeutics, Evelo Therapeutics, Genentech/Roche, Gilead Sciences, GSK, H3 Biomedicine, Hengrui Therapeutics, Hutchison MediPharma, Jacobio, Janssen, Klus Pharma, Kymab, Loxo, LSK Biopartners, Lycera, Macrogenics, Merck, Millennium, Mirati Therapeutics, Moderna Therapeutics, Pfizer, Prelude Therapeutics, Ribon Therapeutics, Seven and Eight Biopharmaceuticals, Syndax, Taiho Pharmaceutical, Tesaro, TopAlliance BioSciences Inc., Vigeo, ORIC, Artios, Treadwell, Mabspace, IgM Biosciences, Puretech, Artios, BioTheryX, Black Diamond Therapeutics, IgM Biosciences, NGM Biopharmaceuticals, Novartis, nurix, Relay Therapeutics, Samumed, Silicon Therapeutics, TeneoBio, Treadwell Therapeutics, Zymeworks, Olema, Adagene, Astellas, NGM, Accutar Biotech, Nurix, Novartis, Compugen, Black Diamond Therapeutics, Relay Therapeutics, Artios, Treadwell Therapeutics, MabSpace Biosciences, Immunogen, Blueprint Pharmaceuticals, Accutar, Artios, Bayer, Bicycle Therapeutics, BioTheryX, Compugen, Cullinan Oncology, Erasca, Inc., Immune-Onc Therapeutics, Immunitas, Jazz Pharmaceuticals, NGM Biopharmaceuticals, Novartis, ORIC Pharmaceuticals, Pionyr, Revolution Medicines, Ribon Therapeutics, Step Pharma, Syndax, Synthorx, Xencor.