Effects of CVA21, an Oncolytic Virus, in Combination with Pembrolizumab on Immunogenicity and the Tumor Microenvironment in Advanced NSCLC: A Phase I/II Trial

Balasubramanian, A; PALMER, J; Marceaux, C; Kanwal, S; Tarasova, I; Batey, D; Senko, C; Asadi, K; Yokote, K; Christie, M; Gunjur, A; Arulananda, S; Parakh, S; Adams, D; Phipson, B; Grimmond, S; Cebon, J; Asselin-Labat, ML; John, T

Author(s): Balasubramanian, A; PALMER, J; Marceaux, C; Kanwal, S; Tarasova, I; Batey, D; Senko, C; Asadi, K; Yokote, K; Christie, M; Gunjur, A; Arulananda, S; Parakh, S; Adams, D; Phipson, B; Grimmond, S; Cebon, J; Asselin-Labat, ML; John, T;
Details: Publication Year 2025-11-14,Volume 31,Issue #22,Page 4644-4654
Journal Title: Clinical Cancer Research
Publication Type: Sep 11
Abstract: PURPOSE: Acquired or de novo resistance to immune checkpoint inhibitors occurs in the majority of advanced non-small cell lung cancers. There is an unmet need to improve outcomes for patients with this condition. Oncolytic viruses represent an attractive treatment approach because of their dual activity in inducing tumor cell lysis directly and potentially augmenting antitumor immunity. In this study, we present the safety, efficacy, and translational findings from a phase I/II single-arm trial utilizing CVA21, an oncolytic coxsackievirus, in combination with pembrolizumab in patients with advanced pretreated non-small cell lung cancers. PATIENTS AND METHODS: We performed paired pre- and posttreatment biopsies in 10 patients who received intravenous CVA21 and pembrolizumab, eight of whom had prior treatment with immune checkpoint inhibitor therapy. Whole-genome sequencing and spatial proteomics were performed to comprehensively characterize the response to CVA21. RESULTS: Combination CVA21/pembrolizumab (anti-PD-1) therapy was well tolerated with no serious treatment-related adverse events. Partial responses were seen in two patients with prior acquired anti-PD-1 resistance and disease stabilization in six patients, giving a clinical benefit rate of 80%. High baseline tumor mutational burden and PD-L1 expression were observed in patients with better response to treatment. Interestingly, an increase in antigen presentation and CD8+ T-cell infiltration was observed on-treatment compared with baseline in patients with better progression-free survival. CONCLUSIONS: This study demonstrates the potential of CVA21 to modulate the immunogenicity of tumor cells and remodel the tumor microenvironment, providing insights for patient selection for trials involving novel immunotherapeutic approaches.
Publisher: AACR
Keywords: Humans; *Antibodies, Monoclonal, Humanized/administration & dosage/adverse; effects/therapeutic use; *Carcinoma, Non-Small-Cell Lung/immunology/therapy/pathology/drug; therapy/genetics; *Tumor Microenvironment/immunology/drug effects; Male; Female; *Lung Neoplasms/immunology/therapy/pathology; Middle Aged; *Oncolytic Viruses/immunology/genetics; Aged; *Oncolytic Virotherapy/methods; Combined Modality Therapy; Immune Checkpoint Inhibitors/administration & dosage
Research Division(s): Personalised Oncology; Bioinformatics and Computational Biology
PubMed ID: 40932352
Publisher's Version: https://doi.org/10.1158/1078-0432.CCR-25-1449
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-09-23 08:17:28

Last Modified: 2025-12-15 01:28:23