Pelareorep Combination Demonstrates Durable Responses in Second-Line RAS-Mutant MSS CRC

Pelareorep (Reolysin) in combination with standard-of-care (SOC) bevacizumab (Avastin) and FOLFIRI (leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride) as second-line therapy led to durable responses in patients with KRAS-mutant, microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), according to updated data from the phase 1 REO 022 trial (NCT01274624).¹

Among patients who received the pelareorep-based combination, the median duration of response (DOR) was 19.5 months. The drug’s developer, Oncolytics Biotech Inc, noted that this outcome is favorable in the context of historical benchmarks of approximately 4 to 6 months. The overall response rate was 33%, numerically greater than historical response rates with SOC alone (6%- 11%).

The update comes as investigators and the FDA are discussing a potential accelerated approval pathway for the intravenously delivered oncolytic virus immunotherapy. In February 2026, the FDA granted a fast track designation to pelareorep plus bevacizumab/FOLFIRI in this same patient population based on data from REO 022.²

“We believe these data demonstrate a compelling durability signal for pelareorep in colorectal cancer,” Jared Kelly, chief executive officer of Oncolytics Biotech, stated in a news release.¹ “A 19.5-month median DOR in second-line patients—representing a 3- to 4-fold improvement over historical expectations—highlights pelareorep’s potential to deliver sustained benefit in a population with few effective options. We believe these results support a path toward accelerated approval in second-line RAS-mutant MSS mCRC, and we are actively engaging with the FDA to align on a regulatory strategy leveraging our ongoing randomized study.”

What is the design of REO 022?

REO 022 is a multicenter, dose-escalation study enrolling patients at least 18 years of age with histologically confirmed colon or rectal cancer, radiologically measurable metastases, and confirmed KRAS mutations.³ Additional eligibility criteria include 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. Notably, patients were not allowed to have previously received FOLFIRI or irinotecan in the metastatic setting or experienced 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 IV bolus and 2400 mg/m² continuous infusion of 5-fluorouracil 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. Key secondary end points included ORR, clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety.

What additional findings were previously reported from this study?

Preliminary survival data showed a median PFS of 16.6 months and a median OS of 27.0 months with the pelareorep-based regimen; outcomes with the SOC were 5.7 months and 11.2 months, respectively.²

Additional readouts from a translational analysis of paired tumor biopsies in REO 022 showed that treatment with pelareorep increased KRAS mutation–specific T-cell populations, suggesting that pelareorep boosts antitumor immune recognition in KRAS-mutant patient populations.⁴ A complete analysis of these translational data will be presented at an upcoming medical meeting.

What is the current status of pelareorep development?

In addition to REO 022, the open-label, multicenter, phase 2 REO 033 trial (NCT07446322) is currently enrolling patients with RAS-mutant MSS mCRC who have progressed after 1 prior line of oxaliplatin-based therapy.⁵ This study will compare pelareorep plus SOC bevacizumab/FOLFIRI with the SOC alone in the second line.

Beyond CRC, pelareorep is being studied in gastrointestinal malignancies, including pancreatic cancer, and has previously shown activity in multiple first-line pancreatic cancer studies, two phase 2 studies in metastatic breast cancer, and early-phase trials in anal cancer.¹

References

1. Oncolytics Biotech reports durable responses in second-line RAS-mutant MSS colorectal cancer. News release. Oncolytics Biotech Inc. May 4, 2026. Accessed May 4, 2026. https://ir.oncolyticsbiotech.com/press_releases/oncolytics-biotech-reports-durable-responses-in-second-line-ras-mutant-mss-colorectal-cancer/
2. Oncolytics Biotech receives FDA fast track designation for pelareorep in 2L KRAS-mutant MSS metastatic colorectal cancer. News release. Oncolytics Biotech Inc. February 4, 2026. Accessed May 4, 2026. https://oncolyticsbiotech.com/press_releases/oncolytics-biotech-receives-fda-fast-track-designation-for-pelareorep-in-2l-kras-mutant-mss-metastatic-colorectal-cancer/
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 May 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 Inc. December 16, 2025. Accessed May 4, 2026. https://oncolyticsbiotech.com/press_releases/oncolytics-biotech-announces-promising-efficacy-and-translational-data-supporting-pelareorep-in-kras-mutant-metastatic-colorectal-cancer/
5. FOLFIRI and bevacizumab with or without pelareorep for second-line treatment of metastatic RAS-mutated, microsatellite-stable colorectal cancer. Updated April 24, 2026. ClinicalTrials.gov Accessed May 4, 2026. https://clinicaltrials.gov/study/NCT07446322?term=NCT07446322&viewType=Card&rank=