FDA Grants Fast Track Designation to Pelareorep in KRAS+ MSS Metastatic CRC

Pelareorep (Reolysin) in combination with bevacizumab (Avastin) and leucovorin, fluorouracil, and irinotecan (FOLFIRI) has earned fast track designation from the FDA as a treatment for patients with microsatellite stable (MSS) metastatic colorectal cancer (CRC) harboring KRAS mutations, according to a press release from the developer, Oncolytics Biotech® Inc.¹

Supporting data for the designation came from the phase 1 REO 022 trial (NCT01274624) evaluating the novel therapeutic combination among those with KRAS-mutant metastatic CRC. Previous findings showed that the pelareorep combination yielded an overall response rate (ORR) of 33%, which exceeded a historical rate of 10% with standard-of-care therapy in this population.

According to additional findings from the REO 022 trial, the median progression-free survival (PFS) was 16.6 months with pelareorep-based therapy vs 5.7 months with standard second-line therapy.² Furthermore, the median overall survival (OS) was 27.0 months with the experimental regimen and 11.2 months with standard second-line treatment.

“This designation is an important validation of our focus on pelareorep’s potential as a platform immunotherapy for gastrointestinal cancers like [CRC]. Adding pelareorep to the standard of care in this underserved segment of [patients with CRC] results in a doubling or tripling of critical clinical endpoints, including [OS], [PFS], and [ORR],” Jared Kelly, chief executive officer at Oncolytics, stated in the press release.¹ “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.”

Developers designed pelareorep as a naturally occurring non-enveloped human reovirus.³ According to the investigators of the REO 022 trial, the specificity of the reovirus for targeting RAS-transformed cells and its relatively nonpathogenic nature in humans may make it a viable anti-cancer therapy candidate.

In the dose-escalation phase 1 study, 36 patients were assigned to receive pelareorep as a 1-hour intravenous infusion on days 1, 2, 3, 4, and 5 every 4 weeks. Investigators also administered irinotecan as a 90-minute intravenous infusion on day 1 every 2 weeks at dose levels ranging from 125 to 180 mg/m², leucovorin as a 2-hour infusion at 400 mg/m² on day 1 every 2 weeks, fluorouracil at 400 mg/m² bolus followed by 2400 mg/m² as a continuous intravenous infusion over 46 hours on day 1 every 2 weeks, and bevacizumab at 5 mg/kg on day 1 every 2 weeks.

The trial’s primary end points included dose-limiting toxicities and pharmacokinetic parameters. Secondary end points included ORR, PFS, OS, clinical benefit rate, and safety and tolerability.

Patients 18 years and older with histologically confirmed cancers of the colon or rectum with radiologically documented and measurable metastases, no prior receipt of FOLFIRI or irinotecan in the metastatic setting, and KRAS-mutated disease were eligible for enrollment on the trial. Other eligibility criteria included having no lasting acute toxicities related to any prior radiotherapy, an ECOG performance status of 0 to 2, and a life expectancy of at least 3 months.

Those with brain metastases; known HIV infection or active hepatitis B or C; receipt of more than 20 Gy of radiation to the pelvis; or receipt of chemotherapy, immunotherapy, hormonal therapy, or major surgery within 28 days of beginning study treatment were ineligible for enrollment. Patients were also unable to enroll on the trial if they had clinically significant cardiac disease, dementia or altered mental status affecting the ability to provide informed consent, or uncontrolled hypertension.

References

1. 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 February 5, 2026. https://tinyurl.com/7br4n9m5
2. Oncolytics Biotech highlights strong efficacy and translational data in metastatic colorectal cancer; will advance regulatory pathway discussions. News release. Oncolytics Biotech Inc. September 8, 2025. Accessed February 5, 2026. 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 February 5, 2026. https://tinyurl.com/bdekvwbp