CV301 and Anti-PD-1 Therapy in Non-Small Cell Lung Cancer

Division Of Basic Sciences - Nci

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Abstract

This study has been completed and the results have been published. PMID: 36054490. Summary: CV301, a poxviral-based vaccine, has been evaluated in a phase 1 clinical trial (NCT02840994) and shown to be safe and immunologically active (phase 1a). Preclinical data support a combination of CV301 with programmed death-1 (PD-1) inhibitors, which has been evaluated in the phase 1b part of this trial reported here. Participants with advanced nonsquamous non-small cell lung cancer (NSCLC) without actionable genomic alterations received two priming doses of modified vaccinia Ankara-BN-CV301 (MVA) four weeks apart, followed by boosting doses of fowlpox-CV301 (FPV) at increasing time intervals for a maximum of 17 doses in combination with nivolumab for cohort 1 (C1) and 15 doses in combination with pembrolizumab for cohort 2 (C2). The primary objective was evaluation of safety and tolerability. Twelve participants were enrolled and received treatment (C1: 4; median age: 64 years). Mean treatment duration was 332 days in C1 and 289 days in C2. CTCAE grade 3 or higher adverse events (AEs) were observed in four (100%) participants in C1 and three (37.5%) participants in C2. There was one death on trial. Immune-related AEs (irAEs) fulfilling criteria for a dose-limiting toxicity included one case of pneumonitis. Among 11 evaluable participants, one (9%) had a complete response, one (9%) had a partial response and nine (82%) had stable disease. This trial showed that CV301 administered with PD-1 inhibitors is safe and clinically active in patients with advanced NSCLC. The frequency or severity of AEs is not increased, including irAEs for each component of the combination.