Oncolytics Launches Pivotal Trial for Hard-to-Treat Colorectal Cancer

SAN DIEGO, CA – March 02, 2026 – In a move that could shift the treatment landscape for a challenging form of cancer, Oncolytics Biotech® Inc. today announced the launch of a randomized Phase 2 clinical trial for its novel immunotherapy, pelareorep. The study, dubbed REO 033, will target patients with metastatic colorectal cancer (mCRC) who have limited options, aiming to confirm earlier, highly promising results and solidify a new path forward for a growing patient population.

The initiation of this controlled study follows a recent U.S. Food & Drug Administration (FDA) decision to grant Fast Track Designation to the pelareorep-based regimen, a significant validation of its potential to address a major unmet medical need. With preliminary data expected by the end of 2026, the trial represents a critical step in determining if this innovative therapy can deliver on its considerable promise.

Confronting a Difficult Diagnosis

Metastatic colorectal cancer remains a formidable public health challenge. For patients whose disease progresses after initial treatment, particularly those with a RAS-mutated, microsatellite-stable (MSS) tumor profile, the prognosis is often poor. This specific subtype is notoriously resistant to many targeted therapies and has historically shown little response to the immune checkpoint inhibitors that have revolutionized other cancer types.

The current standard of care for these second-line patients typically involves a chemotherapy regimen known as FOLFIRI (fluorouracil, leucovorin, irinotecan), often combined with the anti-angiogenic drug bevacizumab. While this provides some benefit, the outcomes are modest, with median overall survival hovering around 11.2 months and progression-free survival at just 5.7 months. The objective response rate, a measure of tumor shrinkage, languishes at approximately 10%.

This stark reality highlights a desperate need for more effective treatments. The problem is compounded by an alarming trend noted by oncologists. “An immunotherapy with the potential to improve outcomes would improve treatment options in colorectal cancer and would be highly welcomed, especially as we are seeing more and more younger patients being diagnosed with colorectal cancer,” said Dr. Van Morris, a member of Oncolytics Biotech's Gastrointestinal Scientific Advisory Board and an Associate Professor at The University of Texas MD Anderson Cancer Center.

Turning 'Cold' Tumors 'Hot'

At the heart of the REO 033 study is pelareorep, a first-in-class immunotherapeutic agent derived from a naturally occurring reovirus. Unlike traditional treatments, pelareorep works through a dual mechanism. First, as an oncolytic virus, it has a natural propensity to selectively infect and destroy cancer cells, particularly those with an activated RAS pathway—the very mutation that makes this form of colorectal cancer so difficult to treat.

More importantly, this viral attack sounds an alarm that awakens the patient's own immune system. The process effectively transforms the tumor microenvironment from immunologically “cold”—ignored by immune cells—to “hot.” The dying cancer cells release signals that attract and activate the body's T-cells, priming them to recognize and attack the cancer throughout the body. This immunomodulatory effect is designed to work in synergy with other cancer therapies, boosting their efficacy.

Oncolytics is leveraging this mechanism by combining pelareorep with the standard FOLFIRI and bevacizumab regimen. The strategy is not to replace the standard of care, but to fundamentally enhance it by turning a suppressive tumor environment into a battlefield where the immune system has the upper hand.

Building on Compelling Early Data

The confidence to launch this pivotal, randomized study stems from the remarkable results of a previous, smaller trial known as REO 022. In that study, patients with the same hard-to-treat mCRC profile received the pelareorep combination therapy and demonstrated outcomes that dramatically surpassed historical benchmarks.

Patients in the REO 022 study achieved a median overall survival of 27 months and a median progression-free survival of 16.6 months. These figures represent a more than doubling of the survival rates typically seen with the standard of care alone. Furthermore, the objective response rate was 33%, a threefold improvement over the expected 10%.

These results are what captured the attention of the FDA and the oncology community. “I am honored to lead this study as I have a long track record working with pelareorep and have witnessed its ability to improve patient outcomes in a meaningful way,” stated Dr. Sanjay Goel, Professor of Medicine at Rutgers Cancer Institute of New Jersey and the Lead Investigator for the new REO 033 trial. “The colorectal cancer data we recorded in the REO 022 study continues to be compelling to this day, as evidenced by the Fast Track Designation, and I hope we can generate additional exciting data in this new trial to support registration.”

A Fast Track to a Potential New Standard

The REO 033 study is designed to provide the robust, controlled data needed for regulatory approval. The trial will enroll 60 patients who have failed first-line, platinum-based chemotherapy. Thirty patients will be randomized to the control arm receiving standard FOLFIRI and bevacizumab, while the other 30 will receive the experimental combination of pelareorep plus FOLFIRI and bevacizumab.

The primary goal is to see if the impressive objective response rate from the earlier study can be replicated in a randomized setting. Secondary endpoints, including progression-free survival and overall survival, will be critical for confirming the therapy's long-term benefit.

The FDA's Fast Track Designation is a crucial component of this strategy. This designation is reserved for therapies that treat serious conditions and fill an unmet medical need. It provides Oncolytics with more frequent communication with the agency and eligibility for a rolling review, which can significantly shorten the path from clinical trial to patient access.

For Oncolytics, a clinical-stage company, the REO 033 trial is a cornerstone of its broader strategy. The company is advancing pelareorep as a platform immunotherapy across multiple gastrointestinal cancers, including pancreatic and anal cancer, where it has also shown promising activity. Success in colorectal cancer would not only provide a transformational new treatment for patients but would also validate the company's entire scientific platform, potentially attracting strategic partnerships to accelerate development and commercialization. If the REO 033 trial successfully confirms the potent efficacy seen in earlier research, it could establish a new standard of care and offer a beacon of hope for thousands of patients facing a difficult prognosis.