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RecruitingInterventionalPhase 2/Phase 3

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

NCT ID: NCT06581406Sponsor: Replimune, Inc.Last updated: 2026-04-02

Summary

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.

Arms & interventions

  • BiologicalRP2

    Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation.

  • BiologicalIpilimumab

    Ipilimumab: human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody

  • BiologicalNivolumab

    Nivolumab: Anti-PD-1 Monoclonal antibody

Outcome measures

Primary

  • Overall Survival (OS)

    OS is the time from the date of randomization to death from any cause.

    Time frame: From Day 1 up to 3 years after last dose.

  • Progression Free Survival (PFS)

    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.

    Time frame: From Day 1 up to 3 years after last dose.

Secondary

  • Number of patients with treatment-emergent adverse events (TEAEs)

    Time frame: 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.

  • Disease Control Rate (DCR)

    Time frame: Every 12 weeks from Day 1 up to 3 years after last dose.

Eligibility criteria

Sex: AllAge: All agesHealthy volunteers: No
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 locations (29)

HonorHealth Research Insisute

Scottsdale, Arizona, 85258

Recruiting
Justin Moser, MD · Contact

UC San Diego Moores Cancer Center

La Jolla, California, 92037

Recruiting
Gregory Daniels, MD · Contact

The Angeles Clinic and Research Institute

Los Angeles, California, 90025

Recruiting
Inderjit Mehmi, MD · Contact

University of California Los Angeles

Los Angeles, California, 90095

Recruiting
Bartosz Chmielowski, MD · Contact

Stanford Cancer Institute

Palo Alto, California, 94304

Recruiting
Allison Betof Warner, MD · Contact

University of Colorado Hospital - Anschutz Cancer Pavilion(ACP)

Aurora, Colorado, 80045

Recruiting
Sapna Pradyuman Patel, MD · Contact

The Melanoma & Skin Cancer Institute

Englewood, Colorado, 80113

Recruiting
Ryan Weight, DO, MS · Contact

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007

Recruiting
Suthee Rapisuwon, MD · Contact

Mayo Clinic - Jacksonville FL

Jacksonville, Florida, 32224

Recruiting
Roxana S. Dronca, MD · Contact

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136

Recruiting
Leonel Fernando Hernandez Aya, MD · Contact

Emory Winship Cancer Institute

Atlanta, Georgia, 30322

Recruiting
Michael Lowe, MD · Contact

Northwestern Memorial Hospital

Chicago, Illinois, 60611

Recruiting
Sunandana Chandra, MD, MS · Contact

University of Chicago Medical Center

Chicago, Illinois, 60637

Recruiting
Daniel Olson, MD · Contact

University of Iowa

Iowa City, Iowa, 52242

Recruiting
Asad Javed, MD · Contact

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting
Kamaneh Montazeri, MD · Contact

Mayo Clinic Rochester

Rochester, Minnesota, 55905

Recruiting
Arkadiusz Z. Dudek, MD · Contact

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting
Alexander Shoushtari, MD · Contact

Duke University Medical Center

Durham, North Carolina, 27710

Recruiting
April Salama, MD · Contact

The Ohio State University

Columbus, Ohio, 43210

Recruiting
Richard Wu, MD, PhD · Contact

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107

Recruiting
Marlana Orloff, MD · Contact

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

Recruiting
Diwakar Davar, MD · Contact

The West Clinic, PLLC dba West Cancer Center

Germantown, Tennessee, 38138

Recruiting
Arnel M. Pallera, MD · Contact

University of Tennessee Medical Center

Knoxville, Tennessee, 37920

Recruiting
Timothy Panella, MD · Contact

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

Recruiting
Meredith Ann McKean, MD, MPH · Contact

Vanderbilt Ingram Cancer Center (Henry-Joyce Cancer Clinic)

Nashville, Tennessee, 37232

Recruiting
Douglas B. Johnson, MD · Contact

UT Southwestern Medical Center

Dallas, Texas, 75390

Recruiting
Sanjay Chandrasekaran, MD · Contact

The University Of Texas Md Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Alexandra Ikeguchi, MD · Contact

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

Recruiting
Natalie Miller, MD, PhD · Contact

University Of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792

Recruiting
Vincent Ma, MD · Contact