FDA Grants Fast Track Designation to Pelareorep Plus Bevacizumab/FOLFIRI in Second-Line KRAS-Mutant mCRC

The FDA has granted fast track designation to the intravenously delivered oncolytic virus immunotherapy pelareorep (Reolysin) in combination with bevacizumab (Avastin) and FOLFIRI (leucovorin, 5-fluorouracil [5-FU], irinotecan) for the treatment of patients with KRAS-mutant, microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) in the second line.¹

The designation was supported by findings from the phase 1 REO 022 trial (NCT01274624), in which the combination produced an overall response rate (ORR) of 33% in patients with MSS mCRC harboring KRAS mutations.^1,2 According to the drug’s developer, Oncolytics Biotech, this response rate compares favorably with a historical ORR of approximately 10% with standard-of-care (SOC) bevacizumab plus chemotherapy alone.

Additionally, early survival data showed that the investigational regimen produced a median progression-free survival (PFS) of 16.6 months and a median overall survival (OS) of 27.0 months; respective outcomes with the SOC alone were 5.7 months and 11.2 months.³

“This designation is an important validation of our focus on pelareorep’s potential as a platform immunotherapy for gastrointestinal cancers like [CRC],” Jared Kelly, chief executive officer of Oncolytics, stated in a news release.¹ “Adding pelareorep to the [SOC] in this underserved segment of colorectal cancer patients results in a doubling or tripling of critical clinical end points, including [OS, PFS, and ORR] in a market that is estimated to be worth several billion dollars. 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.”

What is the design of the phase 1 REO 022 trial?

The multicenter, dose-escalation study enrolled patients at least 18 years of age with histologically confirmed colon or rectal cancer, radiologically measurable metastases, and confirmed KRAS mutations.⁴ Prior exposure to an oxaliplatin-based chemotherapy regimen in the metastatic setting or disease recurrence within 6 months of completion of oxaliplatin-containing adjuvant therapy; an ECOG performance status of 0 to 2; and a minimum life expectancy of 3 months was also required. Patients were not permitted to have received prior FOLFIRI or irinotecan in the metastatic setting, or experience continuing acute toxic effects of prior therapy.

The study comprised cohorts of 3 to 6 patients. Eligible patients were randomly assigned to receive 1 of 4 escalating doses of pelareorep plus SOC in the following dosing schedule:

• Pelareorep: a 1-hour intravenous (IV) infusion on days 1 to 5 of each 4-week cycle.
• Bevacizumab: 5 mg/kg of bevacizumab as a 30-, 60-, or 90-minute IV infusion every 2 weeks.
• FOLFIRI: biweekly administration of a 90-minute IV infusion of irinotecan at 125 mg/m², 150 mg/m², or 180 mg/m²; a 2-hour infusion of 400 mg/m² of leucovorin; and a 400-mg/m² intravenous bolus and 2400-mg/m² continuous infusion of 5-FU over 46 hours.

The study’s primary end points were dose-limiting toxicities to identify the maximum tolerated phase 2 dose, and pharmacokinetic parameters of irinotecan and 5-fluorouracil when combined with pelareorep. Secondary end points included ORR, clinical benefit rate, PFS, OS, and safety.

What additional translational findings were reported from this study?

Results from a translational analysis of paired tumor biopsies in REO 022 showed that treatment with pelareorep increased KRAS-mutation–specific T-cell populations.² This finding indicates that pelareorep may directly bolster antitumor immune recognition in the KRAS-mutant patient population, and provides a biological rationale for developing pelareorep as a precision immunotherapy. The company plans to present a complete analysis of these translational data at an upcoming medical meeting.

What’s next for pelareorep in mCRC?

Based on these phase 1 data, controlled clinical study is planned to compare pelareorep plus the SOC vs SOC therapy alone in second-line KRAS-mutant MSS mCRC.¹ Activation of the first clinical site is expected in March, followed by the activation 10 additional sites shortly thereafter. Interim data from the study are anticipated to read out by the end of 2026.

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. February 4, 2026. https://oncolyticsbiotech.com/press_releases/oncolytics-biotech-receives-fda-fast-track-designation-for-pelareorep-in-2l-kras-mutant-mss-metastatic-colorectal-cancer/
2. 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, 2026. https://oncolyticsbiotech.com/press_releases/oncolytics-biotech-announces-promising-efficacy-and-translational-data-supporting-pelareorep-in-kras-mutant-metastatic-colorectal-cancer/
3. Oncolytics Biotech highlights strong efficacy and translational data in metastatic colorectal cancer; will advance regulatory pathway discussions. News release. Oncolytics Biotech. September 8, 2025. Accessed February 4, 2026. https://oncolyticsbiotech.com/press_releases/oncolytics-biotech-highlights-strong-efficacy-and-translational-data-in-metastatic-colorectal-cancer-will-advance-regulatory-pathway-discussions/
4. 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