A Randomized, Phase 2/3 Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma (RP2-202)

March 31, 2026 updated by: Replimune Inc.

A Randomized, Phase 2/3, Open-Label Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab Versus Ipilimumab in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma

The purpose of this study is to measure the clinical benefits of the combination of RP2 and nivolumab as compared with the combination of nivolumab and ipilimumab in patients with metastatic uveal melanoma who have not been treated with immune checkpoint inhibitor therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

280

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Giuseppe Gullo, MD

Study Locations

  • Australia
    • New South Wales
      • Wollstonecraft, New South Wales, Australia, 2065
        • Recruiting
        • Melanoma Institute Australia
        • Contact:
          • Georgina Long, MD
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Recruiting
        • Peter MacCallum Cancer Centre
        • Contact:
          • Damien Kee, MD
  • United Kingdom
      • London, United Kingdom, SW3 6JJ
        • Recruiting
        • The Royal Marsden NHS Foundation Trust
        • Contact:
          • James Larkin
    • Merseyside
      • Liverpool, Merseyside, United Kingdom, L7 8YA
        • Recruiting
        • The Clatterbridge Cancer Centre NHS Foundation Trust
        • Contact:
          • Joseph Sacco
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • HonorHealth Research Insisute
        • Contact:
          • Justin Moser, MD
    • California
      • La Jolla, California, United States, 92037
        • Recruiting
        • UC San Diego Moores Cancer Center
        • Contact:
          • Gregory Daniels, MD
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California Los Angeles
        • Contact:
          • Bartosz Chmielowski, MD
      • Los Angeles, California, United States, 90025
        • Recruiting
        • The Angeles Clinic and Research Institute
        • Contact:
          • Inderjit Mehmi, MD
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford Cancer Institute
        • Contact:
          • Allison Betof Warner, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Hospital - Anschutz Cancer Pavilion(ACP)
        • Contact:
          • Sapna Pradyuman Patel, MD
      • Englewood, Colorado, United States, 80113
        • Recruiting
        • The Melanoma & Skin Cancer Institute
        • Contact:
          • Ryan Weight, DO, MS
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University Medical Center
        • Contact:
          • Suthee Rapisuwon, MD
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic - Jacksonville FL
        • Contact:
          • Roxana S. Dronca, MD
      • Miami, Florida, United States, 33136
        • Recruiting
        • Sylvester Comprehensive Cancer Center
        • Contact:
          • Leonel Fernando Hernandez Aya, MD
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory Winship Cancer Institute
        • Contact:
          • Michael Lowe, MD
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Medical Center
        • Contact:
          • Daniel Olson, MD
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern Memorial Hospital
        • Contact:
          • Sunandana Chandra, MD, MS
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Contact:
          • Asad Javed, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
          • Kamaneh Montazeri, MD
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Rochester
        • Contact:
          • Arkadiusz Z. Dudek, MD
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Alexander Shoushtari, MD
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Contact:
          • April Salama, MD
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University
        • Contact:
          • Richard Wu, MD, PhD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University
        • Contact:
          • Marlana Orloff, MD
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Hillman Cancer Center
        • Contact:
          • Diwakar Davar, MD
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Recruiting
        • The West Clinic, PLLC dba West Cancer Center
        • Contact:
          • Arnel M. Pallera, MD
      • Knoxville, Tennessee, United States, 37920
        • Recruiting
        • University of Tennessee Medical Center
        • Contact:
          • Timothy Panella, MD
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute
        • Contact:
          • Meredith Ann McKean, MD, MPH
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt Ingram Cancer Center (Henry-Joyce Cancer Clinic)
        • Contact:
          • Douglas B. Johnson, MD
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern Medical Center
        • Contact:
          • Sanjay Chandrasekaran, MD
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center
        • Contact:
          • Alexandra Ikeguchi, MD
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center
        • Contact:
          • Natalie Miller, MD, PhD
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center - University Hospital
        • Contact:
          • Vincent Ma, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Patients who are 18 years of age or older at the time of signed informed consent.
  • Patients with confirmed diagnosis of metastatic Uveal melanoma not amenable to surgical resection.
  • Has at least 1 measurable and injectable tumor of ≥ 1 cm in longest diameter (≥ 1.5 cm in the shortest axis for a lymph node [LN]) that is amenable to serial RP2 injections.
  • Must be willing to provide tumor biopsy samples.
  • LDH ≤ 2 × upper limit of normal (ULN).
  • Has adequate hematologic, hepatic and renal function
  • Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio [INR] ≤ 1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
  • Life expectancy of > 6 months as estimated by the Investigator.

Key Exclusion Criteria:

  • Any exposure to immune checkpoint inhibitor (ICIs) since the time of first being diagnosed with uveal melanoma.
  • Known acute or chronic Hepatitis B or C infection or human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
  • Current active significant herpetic infections or prior complications of HSV-1 infection.
  • Any central nervous system (CNS) involvement of melanoma, including carcinomatous meningitis.
  • Major surgery ≤ 2 weeks prior to the first dose of study intervention.
  • Any bleeding, thrombotic and/or other event that places the patient at an unacceptable risk of complications of intratumoral therapy.
  • Active, known, or suspected autoimmune disease requiring systemic treatment.
  • Prior treatment with an oncolytic virus.
  • Requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
  • Systemic anticancer therapy or prior radiotherapy within 2 weeks of the first dose.
  • Has received Investigation agent within 4 weeks or 5 half-lives (whichever longer) prior to the first dose.
  • Conditions requiring treatment with immunosuppressive doses (> 10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy within 14 days after enrollment.

Additional inclusion/ exclusion criteria are outlined in the study protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Test Arm: RP2 + nivolumab
RP2 (Oncolytic virus) and Nivolumab (programmed death receptor-1 (PD-1) inhibitor)
Biological: RP2
Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation.
Biological: Nivolumab
Nivolumab: Anti-PD-1 Monoclonal antibody
Other Names:
  • Opdivo
Experimental: Control Arm (Active Comparator): ipilimumab + nivolumab
Immune Checkpoint inhibitor combination
Biological: Nivolumab
Nivolumab: Anti-PD-1 Monoclonal antibody
Other Names:
  • Opdivo
Biological: Ipilimumab
Ipilimumab: human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody
Other Names:
  • Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From Day 1 up to 3 years after last dose.
OS is the time from the date of randomization to death from any cause.
From Day 1 up to 3 years after last dose.
Progression Free Survival (PFS)
Time Frame: From Day 1 up to 3 years after last dose.
PFS is the time from randomization to first evidence of confirmed disease progression as assessed by BICR per RECIST 1.1 or death from any cause.
From Day 1 up to 3 years after last dose.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with treatment-emergent adverse events (TEAEs)
Time Frame: From first dose up to 100 days after last dose.
The incidence of all TEAEs.
From first dose up to 100 days after last dose.
Overall Response Rate (ORR)
Time Frame: Every 12 weeks from Day 1 up to 3 years after last dose.
ORR is the proportion of patients with a confirmed best overall response of complete response (CR) or partial response (PR), as assessed by BICR per RECIST v1.1.
Every 12 weeks from Day 1 up to 3 years after last dose.
Disease Control Rate (DCR)
Time Frame: Every 12 weeks from Day 1 up to 3 years after last dose.
DCR is the proportion of patients with a confirmed best overall response of CR, PR, or Stable Disease (SD), as assessed by BICR per RECIST 1.1.
Every 12 weeks from Day 1 up to 3 years after last dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Replimune Inc.

Investigators

  • Study Director: Rahul Marpadga, MD MPH, Replimune Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 17, 2024

Primary Completion (Estimated)

January 1, 2030

Study Completion (Estimated)

October 1, 2031

Study Registration Dates

First Submitted

August 29, 2024

First Submitted That Met QC Criteria

August 29, 2024

First Posted (Actual)

September 3, 2024

Study Record Updates

Last Update Posted (Actual)

April 2, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RP2-202

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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