Oncolytics Reports Preclinical Support for Pelareorep Plus Pan-RAS Inhibitor in Colorectal Cancer

Key Points

• Oncolytics Biotech reported preclinical results evaluating pelareorep with a pan-RAS inhibitor in a RAS-driven colorectal cancer model.
• During the study’s initial every-other-day pelareorep dosing period, the combination reduced tumor growth versus control and showed no evidence that RAS inhibition reduced pelareorep activity.
• After pelareorep dosing shifted to once weekly, the added contribution from pelareorep was less apparent.
• Oncolytics plans additional studies across different dosing schedules and RAS-driven tumor models.
• The findings are preclinical and do not establish that the combination is safe or effective in patients.

Oncolytics Biotech (NASDAQ: ONCY) has reported early laboratory results showing that pelareorep maintained activity when combined with a pan-RAS inhibitor in a colorectal cancer model driven by RAS signaling.

The company said the results support further study of whether pelareorep can complement RAS-targeted treatments, potentially helping deepen or extend treatment responses and delay the development of resistance.

Combination Study Shows No Evidence of Drug Antagonism

During the initial treatment period, researchers administered pelareorep every other day. Pelareorep alone, the pan-RAS inhibitor alone, and the combination all reduced tumor growth compared with the control group.

The greatest tumor reductions occurred in the pan-RAS inhibitor group and the combination-treatment group.

Oncolytics said pelareorep retained activity in the presence of RAS inhibition, with no evidence of antagonism between the two therapies. In other words, the RAS inhibitor did not appear to interfere with pelareorep’s activity during the more frequent dosing period.

Weekly Dosing Produced Less Clear Added Activity

The study later moved from every-other-day pelareorep treatment to a weekly dosing schedule.

After that transition, the additional activity associated with pelareorep became less clear. The company said the finding points to a need to study alternative dose schedules to better understand pelareorep’s contribution to the combination.

Oncolytics plans to evaluate the treatment combination in additional RAS-driven tumor models and with different dosing regimens. The company will assess potential effects on tumor-response depth, response duration, and the emergence of resistance to RAS-targeted therapy.

Pelareorep Is Designed to Combine Direct Tumor Targeting With Immune Activation

Pelareorep is an intravenously administered investigational immunotherapy. It is designed to selectively replicate in tumor cells while activating innate and adaptive immune responses against cancer.

The company said previously published independent research indicates that RAS inhibitors do not interfere with the biological mechanism through which pelareorep selectively infects tumor cells. Oncolytics believes this compatibility may make the combination suitable for further study.

The company also said pelareorep has been administered to more than 1,200 patients and has shown potential in clinical studies to enhance checkpoint inhibitors and other cancer treatments across several solid tumor types.

Next Research Will Focus on Dose Schedule and Resistance

Resistance remains a major challenge for RAS-targeted cancer therapies. Oncolytics believes sustained pelareorep treatment may potentially extend or deepen the effect of RAS inhibition and delay resistance. The company also believes pelareorep could potentially provide an option for patients whose cancer becomes resistant to RAS inhibitors.

Those possibilities remain hypotheses based on preclinical work. The current study does not provide clinical safety, dosing, tumor-response, survival, or resistance data in humans.

Pelareorep has not been approved for colorectal cancer or any other indication. Further laboratory studies and clinical trials will be required to determine whether the combination has a meaningful benefit for patients.