RP2/RP3 in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With CRC

NCT05733611 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: RPL-004
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, Phase 2 clinical trial evaluating therapy with an oncolytic immunotherapy (RP2 or RP3) in combination with atezolizumab and bevacizumab in patients with advanced Microsatellite Stable and Mismatch Repair Proficient Colorectal Carcinoma.

Conditions

pMMR; Refractory Metastatic Colorectal Cancer; MSS

Keywords

Colorectal Carcinoma; Immunotherapy; Immuno-oncology; Oncolytic virus; Oncolytic immuno-gene therapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Percentage of subjects achieving objective response (complete response + partial response).

  From Day 1 to documented progression of disease (up to 3 years)

Secondary Outcomes (6)

• Frequency, Nature, and Severity of TEAEs and SAEs

  From Screening through 60 days after last dose of RP2/RP3, or 135 days after last dose of atezolizumab/bevacizumab

• Overall Survival

  From Day 1 to date of death by any cause (up to 3 years)

• Progression-free Survival

  From Day 1 to documented progression of disease (up to 3 years)

• Duration of Response

  From documented response to documented progression of disease (up to 3 years)

• Duration of Clinical Benefit

  From Day 1 to loss of clinical benefit (up to 3 years)

Study Arms (2)

RP2 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC

EXPERIMENTAL

RP2 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).

Biological: RP2; Biological: atezolizumab; Biological: bevacizumab

RP3 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC

EXPERIMENTAL

RP3 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).

Biological: RP3; Biological: atezolizumab; Biological: bevacizumab

Interventions

RP2 BIOLOGICAL

Genetically modified herpes simplex type 1 virus

RP2 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC

RP3 BIOLOGICAL

Genetically modified herpes simplex type 1 virus

RP3 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC

atezolizumab BIOLOGICAL

anti-PD-L1 monoclonal antibody

RP2 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC; RP3 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC

bevacizumab BIOLOGICAL

anti-VEGF therapy

RP2 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC; RP3 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years of age.
• Histological or cytologic diagnosis of colorectal adenocarcinoma that is unresectable or metastatic.
• Have had disease progression or were intolerant to treatment protocols that included irinotecan and oxaliplatin. Epidermal growth factor receptor (EGFR) or vascular endothelial growth factor receptor (VEGFR) directed therapies are allowed as part of the previous therapy if indicated.
• Has at least 1 measurable tumor of ≥1 cm in longest diameter (or ≥1.5cm shortest diameter for lymph nodes).
• Has injectable tumor(s) of at least 1cm in aggregate total diameter.
• Must be willing to consent to provide archival tumor biopsy samples obtained within 90 days prior to Screening, or a fresh tumor biopsy collected on Day 1 of treatment or earlier.
• Has adequate hematologic function, including:
• White blood cell count ≥2.0 × 10\^9/L
• Absolute neutrophil count ≥1.5 × 10\^9/L
• Platelet count ≥75 × 10\^9/L
• Hemoglobin ≥8 g/dL(transfusions allowed; however, patient must not be transfusion-dependent).
• Has adequate hepatic function, including:
• Total bilirubin ≤1.5 × upper limit of normal (ULN; except patients with Gilbert syndrome or liver metastases, who must have a total bilirubin of \<2.0 × ULN)
• Serum albumin ≥2.8 g/dL
• Aspartate aminotransferase and alanine aminotransferase (ALT)≤3.0 × ULN (or ≤5.0 × ULN, if liver metastases are present).

You may not qualify if:

• Prior treatment with regorafenib, trifluridine/tipiracil, fruquintinib, and immunotherapies.
• Has received more than 3 lines of therapy for CRC.
• Has microsatellite instability-high (MSI-H)/deficient DNA mismatch repair (dMMR)disease or BRAF V600E mutation.
• Acute or chronic hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or acute or chronic hepatitis C virus (HCV; defined as HCV RNA \[qualitative\] is detected).
• Note: Patients who have been effectively treated are eligible for enrollment. Patients must be negative for HBsAg and HCV RNA.
• Known human immunodeficiency virus (HIV) infection.
• Note: Testing for HIV is not required unless mandated by local health authority or clinically indicated.
• Had systemic infection requiring intravenous (IV) antibiotics or other serious infection within 14 days prior to dosing.
• With active significant herpetic infections or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis).
• Note: Patients with sporadic cold sores may be enrolled as long as no active cold sores are present at the time of Day 1
• Active or history of central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Prior malignancy active within the previous 3 years, except for locally curable cancers that have apparently been cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• Macroscopic intravascular invasion into any large blood vessel such as the main portal vein, hepatic vein, pulmonary arteries or veins, aorta, or vena cava.
• Had a significant bleeding event within the last 12 months that places the patient at unjustifiable risk for bleeding from deep intratumoral injection procedures based on Investigator assessment or interventional radiologist assessment.
• History of significant cardiac vascular disease including myocarditis or congestive heart failure (defined as New York Heart Association Functional Classification III or IV), or unstable angina, serious uncontrolled cardiac arrhythmia, or myocardial infarction within 6 months of randomization.

Sponsors & Collaborators

• Replimune Inc.: lead
• Roche Pharma AG: collaborator

Study Sites (2)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of Washington Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Gary Vanasse, MD

  Replimune Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: February 17, 2023
• Study Start: June 29, 2023
• Primary Completion: August 18, 2025
• Study Completion: August 18, 2025
• Last Updated: February 2, 2026

Record last verified: 2026-01

Locations

US (2)