Oncolytics Biotech (Nasdaq: ONCY) has received written feedback from the FDA aligning on a potential pivotal expansion of REO 033, its ongoing randomized study of pelareorep in second-line RAS-mutant, microsatellite stable (MSS) metastatic colorectal cancer — a population with few targeted treatment options and that generally does not benefit from checkpoint inhibitors because of its MSS status.
The San Diego-based company submitted a Type D meeting request asking the FDA whether the existing Part A design of REO 033 could support expansion into a pivotal Part B, and whether Part B could support accelerated approval based on objective response rate (ORR) and duration of response, with progression-free survival (PFS) as the basis for full approval. The FDA's written responses, Oncolytics said, provided alignment on both questions. The agency also suggested an End-of-Phase meeting to finalize key elements of the registration program; Oncolytics elected to forego the scheduled Type D meeting and will pursue that path as the program advances.
Pelareorep is an intravenously delivered oncolytic reovirus that selectively replicates in tumor cells while activating innate and adaptive immune responses, including upregulation of inflammatory cytokines, formation of tertiary lymphoid structures, and expansion of tumor-infiltrating lymphocytes — a mechanism designed to convert immunologically cold MSS tumors into immune-responsive ones.
The REO 033 Part A is a randomized controlled study enrolling 60 patients, comparing pelareorep plus FOLFIRI and Roche's Avastin (bevacizumab) against FOLFIRI and bevacizumab alone. The study was designed from the outset to allow expansion into a pivotal Part B. Oncolytics said it plans to begin Part B start-up activities as soon as positive interim Part A data are available, minimizing the gap between the two stages.
The clinical rationale for the program rests on data from REO 022, a prior study in KRAS-mutant, oxaliplatin-refractory MSS colorectal cancer, which reported a 33% ORR and median DOR of 19.5 months, against a historical ORR benchmark of approximately 6–11% for bevacizumab plus FOLFIRI. PFS reached 16.6 months and OS 27.0 months, also exceeding historical benchmarks cited by the company. Translational analyses showed pelareorep enhanced KRAS-mutant-specific T-cell activity. Pelareorep holds FDA Fast Track designation in this indication.