Pelareorep Exhibits Activity in Second-Line KRAS-Mutated Metastatic CRC

Pelareorep (Reolysin) in combination with standard-of-care (SOC) therapy exhibited improved efficacy as a second-line treatment for patients with KRAS-mutated metastatic microsatellite-stable (MSS) colorectal cancer (CRC), according to a news release from the developer, Oncolytics Biotech.¹

According to previously published findings from the phase 1 REO 022 trial (NCT01274624) evaluating the investigational agent plus SOC therapy consisting of bevacizumab (Avastin) plus leucovorin (folinic acid), 5-fluorouracil, and irinotecan (FOLFIRI), among patients with KRAS-mutated MSS CRC, the objective response rate (ORR) was 33% compared with 6% to 11% with SOC alone. Additionally, the investigational arm exhibited a survival advantage, with a median overall survival (OS) and progression-free survival (PFS) of 16.6 months and 27.0 months vs 5.7 months and 11.2 months with the SOC regimen alone.²

Moreover, a translational analysis of paired tumor biopsies displayed a notable increase in KRAS-mutated-specific T-cell populations with pelareorep, suggesting a direct enhancement of anti-tumor immune recognition among these patients. According to the developers, this KRAS-mutated population may benefit from pelareorep as a precision immunotherapy based on these findings, and they plan to present them at an upcoming medical meeting.

"These results are extremely encouraging. Achieving a 33% ORR in KRAS-mutant MSS colorectal cancer is highly unusual in this setting and warrants immediate further study,” Sanjay Goel, MD, MS, professor of Medicine, Division of Medical Oncology, and Section of Solid Tumor at Rutgers Cancer Institute of New Jersey, said in the news release.¹ “The translational findings strengthen the mechanistic rationale behind the clinical activity we are observing. I am eager to move this program into a controlled study to validate the signal and help bring a much-needed therapeutic option to this patient population."

The phase 1 REO 022 trial enrolled patients with KRAS-mutated metastatic CRC and assigned them to receive 4 escalating doses of pelareorep plus SOC therapy.³ Pelareorep consisted of a 1-hour intravenous infusion on days 1 to 5 of each 4-week cycle. SOC therapy consisted of 5 mg/kg of bevacizumab as a 30-, 60-, or 90-minute infusion every 2 weeks and FOLFIRI, which consisted of: a 90-minute intravenous 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-fluorouracil over 46 hours, all given biweekly.

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

To be eligible for inclusion on the trial, patients 18 years and older had: histologically confirmed colon or rectal cancer and radiologically measurable metastases; prior treatment with an oxaliplatin-based chemotherapy regimen in the metastatic setting or experienced disease recurrence within 6 months of completion of oxaliplatin-containing adjuvant therapy; no prior treatment with FOLFIRI or irinotecan in the metastatic setting; and confirmed KRAS-mutated disease. Additionally, patients must have had no continuing acute toxic effects of prior therapy, an ECOG performance status of 0 to 2, and a minimum life expectancy of 3 months.

"Pelareorep has clearly demonstrated the potential to become a transformational new treatment option in this underserved setting. With translational data supporting its unique activation of KRAS-specific T cells, pelareorep has delivered a 33% [ORR] in KRAS-[mutated], MSS colorectal cancer,” Jared Kelly, chief executive officer of Oncolytics Biotech, concluded.¹

References

1. Oncolytics Biotech® announces promising efficacy and translational data supporting pelareorep in KRAS-mutant metastatic colorectal cancer. News release. Oncolytics Biotech. December 16, 2025. Accessed December 16, 2025. https://tinyurl.com/5n6bjn9x
2. 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 December 16, 2025. https://tinyurl.com/yc839wpx
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 December 16, 2025. https://tinyurl.com/bdekvwbp