Adding pelareorep to FOLFIRI and bevacizumab for second-line RAS‑mutated, MSS metastatic colorectal cancer
An Open-Label, Randomized, Multicentre, Phase 2 Study of FOLFIRI + Bevacizumab + Pelareorep vs. FOLFIRI + Bevacizumab for the Second-Line Treatment of Metastatic, RAS-mutated, Microsatellite-Stable (MSS) Colorectal Cancer
This trial tests whether adding the oncolytic virus pelareorep to standard FOLFIRI plus bevacizumab helps people with RAS‑mutated, microsatellite‑stable metastatic colorectal cancer who progressed after first‑line oxaliplatin therapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Oncolytics Biotech Industry-sponsored |
| Drugs / interventions | bevacizumab, chemotherapy, radiation |
| Locations | 2 sites (Homewood, Alabama and 1 other locations) |
| Trial ID | NCT07446322 on ClinicalTrials.gov |
What this trial studies
This is an open‑label, randomized, multicenter Phase 2 trial that will randomize about 60 patients 1:1 to receive either FOLFIRI plus bevacizumab with pelareorep or FOLFIRI plus bevacizumab alone. The primary endpoint is objective response rate by investigator assessment using RECIST 1.1, with secondary endpoints including overall survival, progression‑free survival, and safety/tolerability. Eligible patients must have histologically confirmed metastatic colorectal cancer with a documented RAS mutation, be microsatellite‑stable (non‑MSI‑H/non‑dMMR), have progressed after an oxaliplatin‑based first line, and have ECOG performance status 0–1. Tumor assessments will be performed after treatment initiation and secondary analyses occur at end of study.
Who should consider this trial
Good fit: Adults with histologically confirmed RAS‑mutated, microsatellite‑stable metastatic colorectal cancer who have measurable disease, progressed after an oxaliplatin‑based first‑line regimen, have ECOG 0–1, and adequate organ function are ideal candidates.
Not a fit: Patients with MSI‑high/dMMR tumors, RAS wild‑type disease, ECOG performance status >1, or those unable to tolerate FOLFIRI or bevacizumab are unlikely to receive benefit from this trial.
Why it matters
Potential benefit: If successful, adding pelareorep could increase tumor response rates and potentially extend progression‑free or overall survival compared with FOLFIRI plus bevacizumab alone.
How similar studies have performed: Early‑phase studies of pelareorep combined with chemotherapy have shown acceptable safety and occasional signals of activity in other cancers, but benefit in RAS‑mutated, MSS metastatic colorectal cancer remains unproven.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Histologically confirmed cancer of the colon or rectum with documented metastasis * Measurable disease per RECIST v. 1.1 * Not candidates for curative surgery or curative radiation * Progressed on, or been intolerant to, a first-line, oxaliplatin-based chemotherapy regimen in the metastatic setting or relapsed within 6 months of completing adjuvant oxaliplatin * Considered medically eligible to receive standard of care (SOC) FOLFIRI with bevacizumab * Non-microsatellite instability high or non-deficient mismatch repair (non-MSI-H/non dMMR) tumor status per a standard local testing method * Tumor confirmed to harbor a known RAS mutation per a standard local testing method * ECOG performance status of 0 or 1 * Patients must have adequate hematological, renal, and hepatic function * Female patients of childbearing potential must have a negative pregnancy test * Life expectancy of at least 6 months Exclusion Criteria: * Undergone systemic chemotherapy, radiotherapy, or surgery, \<4 weeks before study treatment * Ongoing AEs of Grade ≥2 that are related to anti-cancer treatment * Prior treatment with irinotecan * Symptomatic brain metastases * Active autoimmune disease * Receiving immunosuppressive or myelosuppressive medications * Active, uncontrolled infections * Known HIV infection or active hepatitis B or C that requires anti-viral treatment * History of another primary cancer within the last 3 years except for non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ * History of allergy or known hypersensitivity to any of the study drugs, study drug classes, * Uncontrolled or severe cardiac disease * Received any vaccine within 28 days prior to first study treatment
Where this trial is running
Homewood, Alabama and 1 other locations
- Central Alabama Research — Homewood, Alabama, United States (Recruiting)
- Summit Health Cancer Center — Florham Park, New Jersey, United States (Recruiting)
Study contacts
- Study coordinator: Name: Reference Study ID Number: REO 033
- Email: REO-033@oncolytics.ca
- Phone: +1 (858) 247- 7829
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.