1027P - First results for intravenous (IV) VSV-GP (BI 1831169) in patients (pts) with advanced solid tumors from the 1456-0001 study

Background

VSV-GP (BI 1831169), a selective oncolytic virus, generates potent cancer cell oncolysis in vitro and initiates adaptive antitumor immunity in vivo. Here we present the first results for the IV administration of the VSV-GP in pts with advanced solid tumors.

Methods

The 1456-0001 study (NCT05155332) is a Phase I, open-label, dose-escalation study evaluating intratumoral (IT), IV, or IT+IV VSV-GP as monotherapy (Part 1) or in combination with the anti-PD-1 antibody ezabenlimab (Part 2). VSV-GP is given in 21-day cycles, on Days 1 and 4 of Cycle 1, and on Day 1 of Cycles 2–4. Dose finding is guided by the Bayesian Optimal Interval design. Primary endpoint is the number of pts with dose-limiting toxicities (DLTs) during the maximum tolerated dose (MTD) evaluation period (Cycle 1), to determine the MTD and recommended Phase II dose (RP2D). Other endpoints include further safety, efficacy (per immune Response Evaluation Criteria in Solid Tumors [iRECIST]), pharmacokinetics, virus shedding, and immunogenicity.

Results

As of April 10, 2024, VSV-GP IV monotherapy was given to four pts at dose level (DL) 1 and to three pts at DL2. Treatment discontinuations occurred in three pts (DL1, n=2; DL2, n=1) due to disease progression, withdrawal of consent, and administrative cause unrelated to treatment (n=1 each). At DL1, two pts completed all planned treatments, one pt discontinued after two cycles, and one pt discontinued after one dose. At DL2, two pts remain on treatment (three completed cycles, n=1; two completed cycles, n=1). No DLTs were reported. Treatment-related adverse events (TRAEs) were reported in three pts at DL1 and in two pts at DL2. The most frequent (≥30%) Grade 1–2 TRAE in DL1 was cytokine release syndrome (n=2); most frequent in DL2 were decreased neutrophils and influenza-like illness (n=1 each). Grade 3 TRAEs included: lymphopenia (DL1, n=1), neutropenia (DL2, n=1), and increased aspartate aminotransferase (AST) (DL1, n=1; pt had elevated AST at baseline). Two pts on DL1 had stable disease as best overall response (per iRECIST).

Conclusions

The study is ongoing to determine the MTD of IV VSV-GP monotherapy.

Clinical trial identification

NCT05155332.

Editorial acknowledgement

James Meyer, PhD, of Nucleus Global provided writing and editorial support. Boehringer Ingelheim International GmbH was given the opportunity to review the abstract for medical and scientific accuracy as well as intellectual property considerations.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim International GmbH.

Disclosure

M. Oliva Bernal: Financial Interests, Personal, Invited Speaker: Merck, MSD, BMS; Financial Interests, Personal, Advisory Board: Merck, MSD; Financial Interests, Personal, Writing Engagement: MSD; Financial Interests, Personal, Invited Speaker, Teaching activities: MSD, Merck; Financial Interests, Personal, Other, IDMC: Transgene; Financial Interests, Personal and Institutional, Funding: Roche; Financial Interests, Institutional, Local PI: ALX Oncology, MSD, ISA Therapeutics BV, Roche, Ayala Therapeutics, AbbVie, Bayer, Boehringer Ingelheim, Merck, Debiopharm, Seagen, Gilead, BeiGene, Nykode; Financial Interests, Institutional, Funding: GSK; Non-Financial Interests, Institutional, Product Samples: Roche. L. Greillier: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, MSD, Takeda, AbbVie, Novartis, and Pfizer; Financial Interests, Personal, Other, Travel and accommodation expenses: AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, MSD, Takeda, AbbVie, Novartis, and Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, MSD, Takeda, AbbVie, Novartis, and Pfizer. M. Ponz-Sarvise: Financial Interests, Personal, Other, Personal fees: Incyte, Genentech, F. Hoffmann-La Roche, TFS Health Science and AstraZeneca; Financial Interests, Personal, Research Funding: Roche and BMS; Financial Interests, Personal, Other, Travel grants: Incyte and BMS. V. Moreno Garcia: Financial Interests, Personal, Speaker, Consultant, Advisor: Bayer, Basilea Pharmaceuticals, Bristol Myers Squibb, Janssen, Pieris. H. Prenen: Financial Interests, Personal, Other, Honoraria: Amgen, Roche, Sanofi, AstraZeneca, and Bayer. D. Wolf: Financial Interests, Personal, Research Funding: Boehringer Ingelheim, Novartis, Pfizer, AOP, Roche, Bristol Myers Squibb, Merck & Co., and Celgene; Financial Interests, Personal, Speaker, Consultant, Advisor: Boehringer Ingelheim, Novartis, Pfizer, AOP, Gilead, Roche, Bristol Myers Squibb, Merck & Co., and Celgene. A. Quinson, S. Luecke, V. Hern: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. M. Porosnicu: Financial Interests, Personal, Speaker, Consultant, Advisor: Boehringer Ingelheim; Financial Interests, Personal, Research Funding: Boehringer Ingelheim, AstraZeneca, Eli Lilly, Astellas and Sanofi Aventis.