1007P - Systemic STING agonist BI 1703880 plus ezabenlimab in patients (pts) with advanced solid tumors: Initial results from a phase Ia study

Background

BI 1703880 is a novel, systemically administered, next-generation STING agonist with proven antitumor activity in vivo. STING activation is an immunostimulatory approach, which may enhance the activity of standard therapies and improve efficacy. Here, we present initial data, including safety, efficacy, pharmacokinetics, and pharmacodynamics, for BI 1703880 plus ezabenlimab (anti-PD-1 antibody) in pts with advanced solid tumors.

Methods

1480-0001 (NCT05471856) is a Phase I, open-label, non-randomized, dose-escalation study with an innovative lead-in design. All pts receive intravenous BI 1703880 monotherapy in Cycle 1 and in combination with ezabenlimab 240 mg from Cycle 2 onward. BI 1703880 and ezabenlimab are administered for up to 18 and 34 cycles, respectively. The primary endpoint is the occurrence of dose-limiting toxicities (DLTs) during the maximum tolerated dose (MTD) evaluation period. Additional efficacy (per RECIST 1.1), safety and pharmacokinetic/pharmacodynamic endpoints will be assessed.

Results

As of April 24, 2024, 15 pts received treatment at four escalating dose levels. The median number of treatment cycles administered was 2, with 46.7% of pts receiving ≥4 cycles. The median duration of treatment was 36 days (range: 1–358 days). Five pts remain on treatment, with 10 pts discontinuing due to disease progression (n=8) or adverse events (n=2). One pt experienced a DLT (Grade 2 pneumonitis) during the MTD evaluation period. Overall, eight pts have experienced treatment-related adverse events (TRAEs); the most frequent of any grade were pyrexia (n=3) and arthritis (n=2). One pt experienced a Grade 4 TRAE (cystoid macular edema). Efficacy has been observed, including one complete response, one partial response, and three pts with stable disease as of the cutoff date. Increased IFNγ and IP10 were observed in a subset of pts, primarily after Cycle 2. In the pt with a complete response, increased protein and mRNA levels of IFNβ and IP10 were noted after two doses of BI 1703880 during Cycle 1.

Conclusions

The study is ongoing to evaluate DLTs and determine the recommended expansion dose. Clinical benefit has been observed with manageable safety.

Clinical trial identification

NCT05471856.

Editorial acknowledgement

Poppy Mashilo of Nucleus Global provided writing and editorial support.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim International GmbH.

Disclosure

K.J. Harrington: Financial Interests, Personal, Advisory Board: Arch Oncology, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Codiak, Inzen, Merck Serono, MSD, Oncolys, Pfizer, Replimune, and Scenic; Financial Interests, Personal and Institutional, Research Funding: AstraZeneca, Boehringer Ingelheim, MSD, and Replimune. S. Kitano: Financial Interests, Personal, Funding, Personal fees: AstraZeneca, Taiho, Novartis, Sumitomo Pharma, Bristol Myers Squibb, Rakuten Medical, GSK, Merck Biopharma, ImmuniT Research Inc., United Immunity, and PMDA (Pharmaceuticals and Medical Devices Agency); Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim, Pfizer, MSD, and Eisai; grants from Astellas, Ono Pharmaceutical Co., Ltd., Regeneron, Daiichi Sankyo, Chugai, Takeda, Eli Lilly Japan K.K, Gilead Sciences, PACT Pharma, Takara Bio Inc., Incyte, AMED (Japan Agency for Medical Research). V. Gambardella: Non-Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Research Funding: Bayer, Boehringer Ingelheim, and Roche. Institutional funding: Genentech, Merck Serono, Roche, BeiGene, Bayer, Servier, Eli Lilly, Novartis, Takeda, Astellas, Fibrogen, Amcure, Natera, Sierra Oncology, AstraZeneca, MedImmune, Bristol Myers Squibb, and MSD. E.E. Parkes: Non-Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Codiak, and Curadev; Financial Interests, Personal, Research Funding: AstraZeneca. I. Moreno Candilejo: Non-Financial Interests, Personal, Advisory Board, Scientific advisory committees: Ellipses Pharma, Ltd. T. Doi: Financial Interests, Personal, Research Funding: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Rakuten Medical; Financial Interests, Personal, Other, lecture fee: Ono Pharmaceutical Co., Ltd. and Bristol Myers Squibb; Financial Interests, Personal, Funding, research expenses: MSD, Taiho Pharmaceutical, Boehringer Ingelheim, Daiichi Sankyo, Pfizer, Bristol Myers Squibb, AbbVie, Novartis, Eisai, Janssen Pharmaceutical, Sumitomo Dainippon Pharma, Chugai Pharmaceutical, PRA Health Science, Ono Pharmaceutical Co., Ltd., Eli Lilly. D. Berz: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: Jazz Pharmaceuticals, Sun Pharma, Biocept, Dare Bioscience, Oncocyte; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, or speakers’ bureaus and travel support: AstraZeneca, Caris, Jazz Pharmaceuticals, Oncocyte, and Sun Pharma; Financial Interests, Personal, Advisory Board: Biocept and Oncocyte. M. Gutierrez: Financial Interests, Personal, Advisory Board: Sanofi, Incyte, and Boehringer Ingelheim; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy: Guardant; Financial Interests, Personal, Stocks/Shares: COTA/OMI. N. Fernandez, B. Li, J. Barrueco: Non-Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. P. Lorusso: Financial Interests, Personal, Advisory Board: AbbVie, Takeda, Agenus, IQVIA, Pfizer, GSK, QED Therapeutics, AstraZeneca, EMD Serono, Kyowa Kirin Pharmaceutical Development, Kineta Inc., Zentalis Pharmaceuticals, Molecular Templates, ABL Bio, STCube Pharmaceuticals, I-Mab, Seagen, imCheck,; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy: SOTIO, I-Mab, Roivant Sciences, and imCORE Alliance for Roche/Genentech; Non-Financial Interests, Personal, Other, Data monitoring committee: Amgen, DrenBio, and Sotio. All other authors have declared no conflicts of interest.