1026P - Updated results from the phase I 1456-0001 study for intratumoral (IT) VSV-GP (BI 1831169) in patients with advanced solid tumors

Background

VSV-GP (BI 1831169), a novel oncolytic virus derived from vesicular stomatitis virus, demonstrated potent oncolysis of solid cancer cell types and adaptive antitumor immunity in vivo. Initial results from the 1456-0001 study (NCT05155332) suggest IT VSV-GP is well tolerated in patients (n=8) with advanced solid tumors. Here we report updated results for IT VSV-GP monotherapy.

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 the anti-PD-1 antibody 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. Primary endpoint is the number of patients with dose-limiting toxicities (DLTs) during the maximum tolerated dose (MTD) evaluation period, 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 April 10, 2024, 17 patients have received IT VSV-GP monotherapy, four at dose level (DL) 1, seven at DL2, four at DL3, and two at DL4. Most patients received injection into a superficial lesion (n=15), with two patients receiving injection into a deep lesion. Treatment discontinuations occurred in 12 patients (DL1 and DL2 [n=4 each]; DL3 and DL4 [n=2 each]) due to disease progression (n=6), adverse events (Aes; n=4) (unrelated sepsis [Grade 3] and cutaneous vasculitis [Grade 1; n=1 each]; treatment-related neutropenia and cytokine release syndrome [Grade 2, n=1 each]), non-resolution of AE (n=1) and death (n=1). DLTs were reported in the MTD evaluation period only (Grade 3 fatigue and cutaneous vasculitis [n=1 each]). Grade 3 TRAEs were only reported in DL2 (fatigue, lymphopenia, neutropenia and cutaneous vasculitis; n=1 each). Best overall response was stable disease in 8/12 patients with valid tumor assessments, per Response Criteria for Intratumoral Immunotherapy in Solid Tumors.

Conclusions

The study is ongoing to evaluate safety and determine the MTD of IT 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

S. Champiat: Financial Interests, Personal, Financially compensated role, Honoraria: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck KgaA, MSD, Novartis, Roche, Servier; 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, 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 and Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Astex Pharmaceuticals, AstraZeneca AB, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare AG, to-BBB Technologies BV, BeiGene, BicycleTx Ltd, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Casi Pharmaceuticals, Inc., Celgene Corporation, Cellcentric, Chugai Pharmaceutical Co, Cullinan-Apollo, Curevarc, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Therapeutics, GamaMabs, Genentech, GSK, H3 Biomedicine, F. Hoffmann-La Roche AG, Imcheck Therapeutics, Incyte Corporation, Innate Pharma, Institut de Recherche Pierre Fabre, Iris Servier, Iteos Belgium SA, Janssen Cilag, Janssen Research Foundation, Janssen R&D Llc, Kura Oncology, Kyowa Kirin Pharmaceutical Development, Lilly France, Loxo Oncology, MedImmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Molecular Partners AG, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology NV, Oncoethix, Oncopeptides, Orion Pharma, Genomics, Ose Pharma, Pfizer, PharmaMar, Pierre Fabre Medicament, Relay Therapeutics, Inc., Roche, Sanofi Aventis, Seattle Genetics, Sotio, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Transgene, Turning Point Therapeutics, Xencor; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Pfizer, Roche, Sanofi; Non-Financial Interests, Personal and Institutional, Non financial benefits: AstraZeneca, BMS, Boehringer Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. 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. H. Prenen: Financial Interests, Personal, Other, Honoraria: Amgen, Roche, Sanofi, AstraZeneca, and Bayer. 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. H. Bourien: Financial Interests, Personal, Other, Travel and educational support: Amgen. E. Whitman: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Speaker’s Bureau: Merck & Co., Inc., Rahway, NJ, USA, Bristol Myers Squibb, and Regeneron. A. Quinson, S. Luecke, V. Hern: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. U. 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. All other authors have declared no conflicts of interest.