Oncolytics advances the REO 033 trial of pelareorep in RAS-mutant MSS metastatic colorectal cancer as FDA discussions support a potential registrational pathway and Part B expansion.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Oncolytics Biotech has accelerated enrollment activities for its REO 033 clinical trial evaluating pelareorep in combination with FOLFIRI and bevacizumab for patients with second-line RAS-mutant, microsatellite stable (MSS) metastatic colorectal cancer (mCRC). The company also confirmed a Type D meeting with the U.S. Food and Drug Administration (FDA) in August to discuss adding a registration-directed Part B that could support both accelerated and traditional approval within the same study.
REO 033 builds on encouraging findings from the earlier REO 022 study, where pelareorep combined with FOLFIRI and bevacizumab exceeded historical second-line standard-of-care benchmarks for progression-free survival, overall survival, objective response rate, and duration of response. Based on those results, pelareorep previously received FDA Fast Track designation for RAS-mutant MSS metastatic colorectal cancer.
Pelareorep Targets an Immunologically Resistant Form of Colorectal Cancer
Pelareorep is an investigational intravenously administered immunotherapy that stimulates anti-tumor immune responses by increasing inflammatory cytokines, promoting tertiary lymphoid structure formation, and expanding tumor-infiltrating lymphocytes. The approach aims to improve immune recognition in RAS-mutant MSS metastatic colorectal cancer, a subtype that responds poorly to currently available immunotherapies and has limited treatment options after first-line therapy.
Trial Expansion Gains Momentum
REO 033 is a randomized, multi-part clinical study comparing pelareorep plus FOLFIRI and bevacizumab with FOLFIRI and bevacizumab alone in second-line RAS-mutant MSS metastatic colorectal cancer.
The ongoing Part A will enroll approximately 60 patients. Oncolytics reported that about half of the planned clinical sites will be activated by the end of July 2026, with the remaining sites expected to open by the end of August. More than 20 patients have already been pre-identified across participating centers, supporting faster enrollment during the second half of the year.
Enrollment has also opened at Rutgers Cancer Institute of New Jersey under the leadership of global principal investigator Dr. Sanjay Goel.
FDA Discussion Could Streamline Development
The planned FDA Type D meeting will focus on incorporating a larger, registration-directed Part B into the existing REO 033 protocol. According to the company, Part B would retain the current study framework while increasing enrollment and adding blinded independent central review. This approach could generate evidence to support both accelerated approval and full regulatory approval without launching a separate registrational trial.
Dr. Sanjay Goel said the durable efficacy observed in REO 022 justifies evaluation in a randomized study and noted that the rapid expansion of REO 033 across leading academic centers could further clarify pelareorep’s role in RAS-mutant MSS metastatic colorectal cancer.
Chief Executive Officer Jared Kelly said ongoing discussions with the FDA have helped shape a regulatory strategy that builds on the existing trial infrastructure while potentially shortening development timelines without compromising scientific rigor.
Path Forward
Oncolytics expects to report an initial tumor response update from patients enrolled in Part A by the end of 2026. Subject to FDA feedback following the August meeting, enrollment in the registration-directed Part B is expected to begin during the first quarter of 2027.
If successful, REO 033 could provide the randomized clinical evidence needed to support regulatory submissions while advancing pelareorep as a potential immunotherapy option for patients with RAS-mutant MSS metastatic colorectal cancer, an area of persistent unmet medical need.
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About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.