Pelareorep-Based Regimen Shows Durable Activity in RAS-Mutant mCRC

Combining the oncolytic virus pelareorep (Reolysin) with FOLFIRI and bevacizumab (Avastin) showed sustained clinical activity as a second-line treatment for patients with RAS-mutant, microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), according to updated data from the phase 1 REO 022 trial (NCT01274624).¹

The median duration of response was 19.5 months among patients treated with the pelareorep-based combination. This compares with historical expectations of approximately 4 to 6 months in similar second-line populations.¹ In addition, investigators reported an objective response rate (ORR) of 33% with pelareorep plus FOLFIRI and bevacizumab, compared with historical ORRs of approximately 6% to 11% for standard-of-care (SOC) regimens in this setting.

Safety data from the study were not described in detail in the news release announcing the update. However, pelareorep has previously demonstrated a manageable safety profile in earlier clinical studies when combined with chemotherapy and/or immunotherapy, with adverse events generally consistent with the underlying treatment backbone.¹

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

REO 022 Trial Background and Additional Data

The multicenter dose-escalation phase 1 REO 022 study (NCT01274624) evaluated pelareorep combined with SOC bevacizumab plus leucovorin (folinic acid), 5-fluorouracil, and irinotecan (FOLFIRI) chemotherapy in patients with histologically confirmed colon or rectal cancer, radiologically measurable metastases, and confirmed KRAS mutations.²

To enroll in the trial patients were required to have received prior oxaliplatin-based chemotherapy in the metastatic setting or have 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. Exclusion criteria included prior FOLFIRI or irinotecan in the metastatic setting or having experienced continuing acute toxic effects of prior therapy.²

Eligible patients were randomly assigned to receive 1 of 4 escalating doses of pelareorep plus SOC. The study cohorts included 3 to 6 patients each.

Previously reported data from the study showed a median progression-free survival (PFS) of 16.6 months and a median overall survival (OS) of 27.0 months across the study population.³ 

Based on data from the REO 022 trial, the FDA previously granted a fast track designation to pelareorep plus bevacizumab and FOLFIRI as a second-line therapy in patients with KRAS-mutant MSS mCRC.³

Next Steps

Pelareorep is now being study in a randomized trial, the ongoing phase 2 REO 033 study (NCT07446322).⁴ This open-label, multicenter, phase 2 trial currently enrolling patients with RAS-mutant MSS mCRC and disease progression after 1 prior line of oxaliplatin-based therapy. Patients in the trial are being randomized to pelareorep plus standard FOLIFIRI and bevacizumab or the control arm of FOLFIRI and bevacizumab alone.

The targeted enrollment for the study is 60 patients. The primary end point is ORR with key secondary end points including PFS, OS, duration of response, and disease control rate. The estimated primary completion date for the study is August 30, 2027.

REFERENCES

1. Oncolytics Biotech Inc. Oncolytics Biotech® reports durable responses in second-line RAS-mutant MSS colorectal cancer. Published May 4, 2026. Accessed May 4, 2026. https://tinyurl.com/3hefupde

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 February 4, 2026. https://tinyurl.com/vy68paha

3. Oncolytics Biotech® receives FDA fast track designation for pelareorep in 2L KRAS-mutant MSS metastatic colorectal cancer. News release. Oncolytics Biotech. February 4, 2026. Accessed May 4, 2020. https://tinyurl.com/3kjy9z8m

4. FOLFIRI and bevacizumab with or without pelareorep in metastatic colorectal cancer (NCT07446322). Updated April 24, 2026. Accessed May 4, 2026. https://tinyurl.com/2fxkem7z