Oncolytics Biotech® Aligns with FDA on Pivotal Phase 3 Study Design for Pelareorep in First-Line Metastatic Pancreatic Cancer
Oncolytics Biotech® Inc. (Nasdaq: ONCY) (“Oncolytics” or the “Company”), a clinical-stage immunotherapy company advancing pelareorep, announced that it has reached alignment with the U.S. Food and Drug Administration (FDA) on the key design components of its planned pivotal clinical trial in metastatic pancreatic ductal adenocarcinoma (mPDAC). The study will evaluate pelareorep in combination with standard-of-care chemotherapy—with or without the addition of a checkpoint inhibitor—in the first-line treatment setting.
This agreement follows a recently completed FDA Type C meeting, in which the regulatory agency reviewed and supported the Company’s proposed Phase 3 framework. The upcoming pivotal study is designed to compare traditional chemotherapy (gemcitabine plus nab-paclitaxel) to two investigational regimens that incorporate pelareorep. According to Oncolytics, this alignment provides a clear regulatory pathway to initiate what the Company believes will be the first—and currently only—pivotal immunotherapy study in mPDAC using a viral immunotherapy approach.
Pancreatic cancer remains one of the most aggressive and lethal malignancies worldwide, with exceptionally limited treatment options, particularly in metastatic disease. Immunotherapies, which have revolutionized outcomes in several other tumor types, have shown limited benefit in pancreatic cancer due to its profoundly immunosuppressive tumor microenvironment. Oncolytics aims to change this trajectory with pelareorep, an intravenously administered immunotherapeutic virus that has demonstrated the ability to prime anti-tumor immune responses, remodel the tumor microenvironment, and enhance the activity of checkpoint inhibitors and chemotherapy.
Regulatory Alignment Marks a Major Milestone
“We now have regulatory clarity to allow us to start a pivotal study and ultimately the chance to bring the first approved immunotherapy treatment option to the pancreatic cancer treatment landscape,” said Jared Kelly, Chief Executive Officer of Oncolytics Biotech. “The data speaks for itself, but we want to sincerely thank the FDA for its great work in helping us clear this initial regulatory hurdle. Although we still have work to do, we are laser-focused on bringing potential treatments to pancreatic cancer patients who desperately need more options.”
Kelly emphasized that regulatory alignment represents a critical step for any late-stage development program, especially for a disease area in which incremental survival benefits can translate to meaningful clinical impact. By receiving feedback and concurrence on the major elements of its study design, Oncolytics can now intensify preparations for launch, including the completion of the full study protocol, a comprehensive statistical analysis plan, and operational planning across trial sites.
Details of the Pivotal Study Design
The Phase 3 trial will comprise three arms:
- Control Arm:
- Gemcitabine plus nab-paclitaxel (GnP), which remains the standard first-line regimen for many patients with metastatic pancreatic cancer.
- Experimental Arm 1:
- GnP plus pelareorep.
- Optional Experimental Arm 2:
- GnP plus pelareorep plus a programmed death-1 (PD-1) or programmed death-ligand-1 (PD-L1) checkpoint inhibitor (CPI).
The inclusion of an optional triple-combination arm provides flexibility and ensures that the study can reflect the rapidly evolving checkpoint inhibitor landscape. Pelareorep has been evaluated in combination with multiple CPIs—including atezolizumab, pembrolizumab, nivolumab, and retifanlimab—and has demonstrated safety and encouraging immune-activation profiles in gastrointestinal cancers and other tumor types. The Company noted that the final CPI selection will be informed by internal assessment and ongoing partnership discussions.
The primary endpoint of the trial will be overall survival (OS), the gold-standard endpoint for regulatory approval in metastatic solid tumors. Secondary endpoints include progression-free survival (PFS) and objective response rate (ORR), which provide additional measures of clinical benefit. Consistent with regulatory expectations for pivotal oncology trials, the study will be statistically powered to detect a clinically meaningful improvement in survival.
To support an accelerated development timeline, the protocol may include an interim analysis, allowing for the potential of expedited review should early signals of efficacy emerge. Notably, either of the experimental arms — or potentially both — could satisfy the success criteria required for registration.
FDA Feedback Validates Clinical and Statistical Approach
Dr. Thomas Heineman, Chief Medical Officer of Oncolytics, underscored the significance of the FDA’s feedback:
“The FDA’s feedback confirms that our design is appropriate to support registration if successful. We are now completing the administrative activities necessary to initiate the study, including finalizing the protocol, generation of supporting documents, and site selection. We also plan to announce the lead principal investigator once these preparations are complete.”
According to Dr. Heineman, receiving clear regulatory validation for the statistical design, study arms, selected endpoints, and overall developmental strategy de-risks a major portion of the Company’s clinical plan. This clarity enables Oncolytics to proceed confidently into the operational phase, which includes:
- Final protocol refinement
- Preparation of investigator and patient-facing documents
- Completion of regulatory documentation
- Selection and activation of clinical sites
- Engagement with contract research organizations (CROs)
- Initiation of investigator meetings and site trainings
The Company noted that site selection is already underway, with a focus on high-volume academic centers and cancer institutes with expertise in pancreatic cancer and immunotherapy research.
The Role of Pelareorep in Pancreatic Cancer Therapy
Pelareorep is an intravenously delivered oncolytic immunotherapy derived from the unmodified reovirus. Unlike genetically modified oncolytic viruses, pelareorep relies on inherent viral properties to selectively infect and replicate within cancer cells while activating both innate and adaptive anti-tumor immune responses. Its mechanism of action includes:
- Triggering an inflamed, immunogenic tumor microenvironment
- Enhancing tumor antigen presentation
- Stimulating T-cell infiltration and activity within tumors
- Increasing tumor susceptibility to checkpoint inhibitors
- Synergizing with chemot
- herapy to improve tumor cell killing
In previous pancreatic cancer studies, pelareorep has shown encouraging signs of clinical activity when combined with chemotherapy and immunotherapy, including evidence of immune modulation and improved survival outcomes in selected patient subgroups. These findings helped inform the design of the pivotal program and support the rationale for combining pelareorep with GnP and potentially with a CPI.
Given the historically limited success of immunotherapies in pancreatic cancer, pelareorep’s multimodal mechanism could represent a meaningful breakthrough if confirmed in the Phase 3 study.
Next Steps and Anticipated Milestones
Oncolytics is currently advancing multiple study start-up activities in preparation for full trial initiation. These steps include:
- Finalization of the regulatory-aligned protocol
- Institutional review board (IRB) and ethics committee submissions
- Execution of clinical trial agreements with selected sites
- Establishment of trial logistics, drug supply planning, and data management frameworks
- Announcement of the lead principal investigator and participating study centers
The Company has committed to providing periodic public updates as milestones are reached. While the exact study launch date was not disclosed, Oncolytics emphasized that it is moving rapidly to initiate the trial following completion of these administrative, clinical, and regulatory processes.
A Pivotal Step in Addressing a High-Unmet-Need Cancer
Pancreatic ductal adenocarcinoma remains one of the deadliest cancer diagnoses, with less than 10% of patients surviving five years after diagnosis. Most patients present with advanced or metastatic disease, and despite decades of research, few transformative treatments have emerged.
By securing alignment with the FDA on its pivotal study design, Oncolytics Biotech has crossed a critical threshold in developing a novel treatment approach for a cancer type in urgent need of innovation. Should pelareorep demonstrate a significant improvement in survival, it could become the first immunotherapy of its kind approved for metastatic pancreatic cancer — a landmark achievement for the Company and, more importantly, for patients and families affected by this devastating disease.
Oncolytics reiterated its commitment to advancing pelareorep through rigorous clinical evaluation and expressed optimism about the potential impact of the pivotal study. The Company will continue to share updates as trial preparations progress and looks forward to initiating the Phase 3 program designed to reshape the therapeutic landscape of metastatic pancreatic cancer.
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