FOLFIRI and Bevacizumab With or Without Pelareorep for Second-Line Treatment of Metastatic RAS-Mutated, Microsatellite-Stable Colorectal Cancer

NCT07446322 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: REO 033
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label, randomized, multicenter Phase 2 study to assess the efficacy and safety of FOLFIRI + bevacizumab + pelareorep vs. FOLFIRI + bevacizumab in patients with RAS-mutated, MSS mCRC who have progressed after one prior line of oxaliplatin-based therapy.

Conditions

Ras-mutated Metastatic Colorectal Cancer; mCRC; MSS Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Proportion of patients with complete response \[CR\], partial response \[PR\] assessed by the investigators and/or central reader according to RECIST v1.1

  At week 8

Secondary Outcomes (4)

• Overall Survival (OS) -

  From the date of randomization through long term follow up at two years

• Progression Free Survival (PFS)

  From randomization to objective progression or death from any cause, whichever occurs first, up to two years

• Disease Control Rate (DCR)

  From randomization to disease progression or death from any cause, whichever occurs first, up to two years

• Duration of Response (DOR)

  From randomization to disease progression or death from any cause, whichever occurs first, up to two years

Study Arms (2)

Arm A

EXPERIMENTAL

Drug: Bevacizumab; Drug: FOLFIRI; Drug: Pelareorep

Arm B

EXPERIMENTAL

Drug: Bevacizumab; Drug: FOLFIRI

Interventions

Bevacizumab DRUG

Bevacizumab (5 mg/kg) IV infusion

Also known as: Avastin

Arm A; Arm B

FOLFIRI DRUG

irinotecan (180mg/m2), leucovorin 400 mg/m2 ± 5-FU (400 mg/m2) IV infusion

Arm A; Arm B

Pelareorep DRUG

pelareorep 4.5 x 10\^10 TCID50 IV infusion

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oncolytics Biotech: lead

Study Sites (3)

Central Alabama Research

Homewood, Alabama, 35209, United States

RECRUITING

Summit Health Cancer Center

Florham Park, New Jersey, 07932, United States

RECRUITING

Gabrail Cancer Center

Canton, Ohio, 44718, United States

RECRUITING

MeSH Terms

Interventions

Bevacizumab; IFL protocol; reolysin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Name: Reference Study ID Number: REO 033

CONTACT

+1 (858) 247- 7829; REO-033@oncolytics.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 3, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): April 30, 2030
• Last Updated: June 8, 2026

Record last verified: 2026-06

Locations

US (3)