137P - First-in-human results from a Phase I dose-escalation study of VSV-GP (BI 1831169) in patients with advanced solid tumors

Background

VSV-GP (BI 1831169) is a selective oncolytic virus that can mediate potent oncolysis in many solid cancer cell types and initiate adaptive antitumor immunity in animal models. Here we report the preliminary first-in-human results of VSV-GP monotherapy administered intratumorally (IT) in patients with advanced solid tumors.

Methods

In this phase I, open-label, dose-escalation study, VSV-GP is administered IT, intravenously (IV) or IT+IV as monotherapy (Part 1) or with anti-programmed cell death 1 compound ezabenlimab (Part 2). VSV-GP is given on Days 1 and 4 of Cycle 1 and Day 1 of Cycles 2–4 (21-day cycles). Dose finding is guided by the Bayesian Optimal Interval design. The primary endpoint is the number of patients with dose-limiting toxicities (DLTs) during the maximum tolerated dose (MTD) evaluation period in order to determine the MTD and/or recommended Phase II dose (RP2D). Further safety, efficacy, pharmacokinetics, shedding and immunogenicity results will be evaluated.

Results

As of August 2, 2023, eight patients have received VSV-GP monotherapy IT, four at dose level (DL) 1 (5 x 10⁷ TCID₅₀) and four at DL2 (5 x 10⁸ TCID₅₀). At DL1, all patients discontinued treatment (progressive disease n=3, unrelated Grade [G] 3 E. coli sepsis n=1). A G1 classified cytokine release syndrome (presenting as fever and low oxygen saturation) was reported in one patient at DL2 following the first dose. The maximum number of cycles received was three. At DL2, one patient discontinued treatment due to related G3 neutropenia after the first administration and three patients are ongoing. One per protocol DLT (G3 fatigue) was reported at DL2 and three additional patients will be recruited. The most frequent related adverse events reported were pyrexia, chills and decreased lymphocytes (Table). Table: 137P

Conclusions

The study is ongoing to evaluate the safety and determine the RP2D of VSV-GP administered IT, IV and IT+IV as monotherapy and in combination with ezabenlimab.

Clinical trial identification

NCT05155332.

Editorial acknowledgement

Katerina Douka, PhD and Devon Else, BSc, of MediTech Media provided writing and editorial support which was contracted by Boehringer Ingelheim International GmbH (BI). BI 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 International GmbH.

Funding

Boehringer Ingelheim International GmbH.

Disclosure

S. Champiat: Financial Interests, Personal, Principal Investigator: AbbVie, Amgen, Boehringer Ingelheim, Cytovation, Eisai, GSK, Imcheck Therapeutics, Immunocore, Molecular Partners Ag, MSD, Ose Immunotherapeutics, Pierre Fabre, Replimune, Roche, Sanofi Aventis, Seagen, Sotio A.S, Transgene; Financial Interests, Personal, Advisory Board: Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, BioNTech, Celanese, Domain Therapeutics, Ellipses Pharma, Genmab, Immunicom, Inc., Nanobiotix, Nextcure, Oncovita, Pierre Fabre, Seagen, Takeda, Tatum Bioscience, Tollys, UltraHuman8; Financial Interests, Personal, Other, Travel and congress: Amgen, AstraZeneca, Bristol Myers Squibb, MSD, Ose Immunotherapeutics, Roche, Sotio; Financial Interests, Personal, Other, Honoraria: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck KGaA, MSD, Novartis, Roche and Servier; Financial Interests, Institutional, Principal Investigator, As part of the Drug Development Department (DITEP): AbbVie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, BeiGene, BicycleTx Ltd, Blueprint Medi; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP): AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Non-financial benefits, Drug supplied: AstraZeneca, BMS, Boehringer Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. N. Wagle: Financial Interests, Institutional, Research Funding: Bavarian Nordic, Bayer, Biocept, Boehringer Ingelheim, Caris MPI, CNS Pharmaceuticals, EpicentRx, Novocure, Oblato, Pyramid Biosciences, Stemedica Cell Technologies, xCures, Xoft. U.M. Lauer: Financial Interests, Institutional, Research Funding: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Speaker, Consultant, Advisor: Boehringer Ingelheim, Abalos Therapeutics; Financial Interests, Personal, Advisory Board: Asgard Therapeutics. 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, Sanofi-Aventis.