Pelareorep Earns FDA Fast Track for Second-Line KRAS-Mutant Metastatic CRC

The FDA has granted fast track designation to the investigational oncolytic virus immunotherapy pelareorep (Reolysin) in combination with bevacizumab (Avastin) and FOLFIRI (leucovorin, fluorouracil, irinotecan) chemotherapy for the second-line treatment of patients with KRAS-mutant, microsatellite-stable (MSS) metastatic colorectal cancer.¹

Pelareorep is an oncolytic reovirus with a twofold mechanism of action. It selectively kills tumor cells, leading to direct viral oncolysis, while stimulating an antitumor immunologic activity to enhance tumors’ response to checkpoint blockade therapy.² The agent has so far shown promise across a range of gastrointestinal cancers in the metastatic setting, including colorectal cancer, pancreatic ductal adenocarcinoma, and most recently anal cancer.

“This designation is an important validation of our focus on pelareorep’s potential as a platform immunotherapy for gastrointestinal cancers like colorectal cancer,” said Jared Kelly, CEO of sponsor Oncolytics Biotech, in a news release.¹ “Adding pelareorep to the standard-of-care in this underserved segment of patients [with colorectal cancer] results in a doubling or tripling of critical clinical end points... Pelareorep offers the potential to help a meaningful number of patients, and I look forward to continuing to collaborate with the FDA to address this treatment gap as expeditiously as possible.”

The REO 022 Trial: Overview and Clinical Data

The efficacy signals supporting this designation were reported from the completed phase 1 REO 022 trial (NCT01274624), which evaluated the safety and preliminary efficacy of the pelareorep combination in patients with platinum-refractory, second-line KRAS-mutant metastatic colorectal cancer.³ Pelareorep was administered via intravenous infusion for 1 hour on days 1 through 5 every 4 weeks.

In this dose-escalation study, the objective response rate (ORR) among patients treated with the pelareorep combination was 33%, more than tripling the approximately historical 10% ORR observed with standard-of-care therapy.⁴

Furthermore, the population achieved a median progression-free survival of 16.6 months, topping the historical standard-of-care figure of 5.7 months. The median overall survival reached 27.0 months, more than double the 11.2 months typically observed with standard second-line regimens.

These outcomes show potential to address a critical unmet need in gastrointestinal oncology. While patients with microsatellite instability-high tumors have benefited from checkpoint inhibitors, many metastatic CRC cases are MSS, which are immunologically "cold" and have historically shown minimal response to immune-based therapies.

Advancing Pelareorep’s Clinical Development

According to Oncolytics Biotech, a controlled clinical trial evaluating the pelareorep combination vs standard of care alone in this patient population is expected to launch in March, with interim data expected by the end of the year. Data from this trial will be key to further confirming the early efficacy signals observed in the early-stage trial and advancing pelareorep’s path toward regulatory approval.

Through more frequent communication pathways with the FDA and potential eligibility for accelerated approval and priority review, the fast track designation will help streamline pelareorep’s development and facilitate a faster regulatory path for patients in need.

REFERENCES

1. Oncolytics Biotech® receives FDA fast track designation for pelareorep in 2L KRAS-mutant MSS metastatic colorectal cancer. News release. Oncolytics Biotech. February 4, 2026. Accessed February 4, 2026. https://tinyurl.com/3kjy9z8m

2. Collienne M, Loghmani H, Heineman TC, Arnold D. GOBLET: a phase I/II study of pelareorep and atezolizumab +/- chemo in advanced or metastatic gastrointestinal cancers. Future Oncol. 2022;18(26):2871-2878. doi:10.2217/fon-2022-0453

3. Study of REOLYSIN® in combination with FOLFIRI and bevacizumab in FOLFIRI-naive patients with KRAS mutant metastatic colorectal cancer. ClinicalTrials.gov. Updated December 19, 2018. Accessed February 4, 2026. https://clinicaltrials.gov/study/NCT01274624

4. Oncolytics Biotech® announces promising efficacy and translational data supporting pelareorep in KRAS-mutant metastatic colorectal cancer. News release. Oncolytics Biotech. December 16, 2025. Accessed February 4, 2025. https://tinyurl.com/4rxrnvmb