Pelareorep Offers Promise in Second-Line KRAS-Mutant Metastatic CRC

Pelareorep (Reolysin), an intravenously delivered oncolytic virus immunotherapy, has demonstrated positive second-line clinical activity as combination therapy in KRAS-mutant, microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), representing an encouraging advancement in a patient population that often responds poorly to treatment.¹

The completed phase 1 REO 022 trial (NCT01274624), which evaluated pelareorep combined with standard-of-care (SOC) bevacizumab (Avastin) plus leucovorin (folinic acid), 5-fluorouracil, and irinotecan (FOLFIRI) chemotherapy,² demonstrated promising clinical activity with the regimen. A 33% objective response rate (ORR) was achieved among patients harboring KRAS mutations and MSS disease, comparing favorably to the historical ORR of 6–11% with SOC treatment alone.

Early survival data also showed notable improvements in progression-free survival (PFS) and overall survival (OS).³ With the investigational regimen, the median PFS was 16.6 months and median OS 27.0 months, compared with the SOC median PFS of 5.7 months and median OS of 11.2 months.

As mechanistic support for the observed responses, a translational analysis of paired tumor biopsies found that KRAS–mutant-specific T-cell populations increased upon treatment with pelareorep. This growth may suggest enhanced immune recognition, reinforcing the capability of the treatment to precisely target the mutated tumors. Complete data from this analysis will be shared at an upcoming medical meeting, according to pelareorep developer Oncolytics Biotech.

Based on the data, the next steps for pelareorep include a controlled study in second-line KRAS-mutant MSS mCRC following pending discussions with regulatory authorities. This trial will be critical for confirming the benefits observed in the phase 1 trial and laying the groundwork for potential registration in mCRC.

“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,” said Sanjay Goel, MD, MS, professor of Medicine at Rutgers Cancer Institute of New Jersey, in a news release.¹ “The translational findings strengthen the mechanistic rationale behind the clinical activity we’re 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.”

Pelareorep: Investigational Combinations and Indications

Along with colorectal cancer, pelareorep is the subject of clinical investigation across various gastrointestinal cancers and breast cancer, where it has demonstrated promising efficacy and safety in combination with other agents.

In the phase 1/2 GOBLET study (REO 029; Eudra-CT: 2020-003996-16), pelareorep in combination with atezolizumab (Tecentriq) was evaluated in the frontline mCRC setting as well as in advanced pancreatic and anal cancers. The safety run-in portion of this study confirmed pelareorep’s favorable safety profile in mCRC.

Additionally, pelareorep has undergone further evaluation in metastatic pancreatic cancer in the REO 017 (NCT00998322) study, where outcomes with pelareorep treatment again exceeded SOC efficacy benchmarks.

In breast cancer, 2 randomized studies in hormone receptor-positive/HER2-negative metastatic breast cancer, IND.213 (NCT01656538) and BRACELET-1 (NCT04215146), reported survival improvements with pelareorep plus SOC chemotherapy, underscoring the broad therapeutic applicability of pelareorep beyond the gastrointestinal system.

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 17, 2025. https://tinyurl.com/4rxrnvmb

2. 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 17, 2025. https://clinicaltrials.gov/study/NCT01274624

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 December 17, 2025. https://tinyurl.com/4sn8eet8