New clinical data from two early-stage trials targeting the signal regulatory protein α (SIRPα) innate immune checkpoint will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 – June 3, 2025, in Chicago, IL, USA.
In a Phase 1b study conducted by Boehringer, its potential, first-in-class SIRPα monoclonal antibody, BI 765063, demonstrated a manageable safety profile as well as preliminary signs of immune activation and additive antitumor activity when combined with PD-1 inhibitor ezabenlimab and cetuximab in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).[1]
Additionally, in an open-label, Phase I trial conducted by Boehringer, its next-generation SIRPα monoclonal antibody, BI 770371, alone and in combination with the PD-1 inhibitor ezabenlimab, was shown to be well tolerated in patients with advanced solid tumors. There were no dose-limiting toxicities in either treatment arm, and the maximum tolerated dose was not reached in either group.[2]
“The preliminary results from these early-stage programs are encouraging and further strengthen Boehringer’s robust immuno-oncology pipeline aimed at accelerating next-generation cancer therapies to address high unmet patient needs,” said Mike Akimov, Head of Medicine, Therapy Area Oncology at Boehringer Ingelheim.
“Boehringer is developing various complementary approaches to activate the immune system against cancer cells and SIRPα blockade paired with a PD-1 inhibitor is a promising strategy. We look forward to seeing if this dual activation may lead to a broader and more sustained anti-tumor response as the programs progress.”
BI 765063 and BI 770371 are designed to block the “don’t eat me” signal that cancer cells use to hide from the immune system. By targeting SIRPα, these antibodies help immune cells like macrophages recognize and destroy tumor cells, bolstering the body’s natural defenses.[3]
Both antibodies have been developed in partnership with OSE, with Boehringer solely responsible for future clinical development and commercialization. Boehringer will move forward with the improved next generation SIRPα inhibitor antibody BI 770371, which will be included a Phase 1b study.
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Presentation Details
Title: An Open-Label, Phase Ib Trial of the SIRPα Inhibitor BI 765063 in Combination with the PD-1 Inhibitor Ezabenlimab and Cetuximab in Patients (pts) with Head and Neck Squamous Cell Carcinoma
Abstract Number: 6019
Session Type/Title: Rapid Oral Abstract – Developmental Therapeutics – Immunotherapy
Date/Time: 01 June 2025 – 11:30am – 1:30pm CDT
Title: An Open-label, Phase I Trial of the SIRPα Monoclonal Antibody, BI 770371, Alone and in Combination with the PD-1 Inhibitor Ezabenlimab in Patients with Advanced Solid Tumors
Abstract Number: 2515
Session Type/Title: Rapid Oral Abstract – Developmental Therapeutics – Immunotherapy
Date/Time: 01 June 2025 – 11:15am – 12:45pm CDT
Reference
[1] An open-label, phase Ib trial of the SIRPα inhibitor BI 765063 in combination with the PD-1 inhibitor ezabenlimab and cetuximab in patients (pts) with head and neck squamous cell carcinoma. – ASCO
[1] An open-label, phase I trial of the SIRPα monoclonal antibody, BI 770371, alone and in combination with the PD-1 inhibitor ezabenlimab in patients with advanced solid tumors. – ASCO
[3] Ring NG, Herndler-Brandstetter D, Weiskopf K, Shan L, Volkmer JP, George BM, Lietzenmayer M, McKenna KM, Naik TJ, McCarty A, Zheng Y, Ring AM, Flavell RA, Weissman IL. Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity. Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):E10578-E10585. doi: 10.1073/pnas.1710877114. Epub 2017 Nov 20. PMID: 29158380; PMCID: PMC5724266.
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