Recruiting
Phase 2
Phase 3

RP2 & Nivolumab

Sponsor:

Replimune Inc.

Code:

NCT06581406

Conditions

Metastatic Uveal Melanoma

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

RP2

Ipilimumab

Nivolumab

Study Details

Brief 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.

Conditions

Metastatic Uveal Melanoma

Study ID

NCT06581406

Start date

Dec 17, 2024

Status verified date

Mar, 2026

Completion date

Oct, 2031

Anticipated

Primary completion date

Jan, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

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 Design

Enrollment

280 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Test Arm: RP2 + nivolumab

RP2 (Oncolytic virus) and Nivolumab (programmed death receptor-1 (PD-1) inhibitor)

experimental: Control Arm (Active Comparator): ipilimumab + nivolumab

Immune Checkpoint inhibitor combination

Interventions

RP2

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

Ipilimumab

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

Nivolumab

Nivolumab: Anti-PD-1 Monoclonal antibody

Primary outcome measure

  • Overall Survival (OS) [ Time Frame: 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. ]

Central Contacts and Locations

Central contacts

Clinical Trials at Replimune

1-781-222-9570Clinicaltrials@replimune.com

Locations

HonorHealth Research Insisute

Recruiting

Scottsdale, Arizona, United States, 85258

UC San Diego Moores Cancer Center

Recruiting

La Jolla, California, United States, 92037

The Angeles Clinic and Research Institute

Recruiting

Los Angeles, California, United States, 90025

University of California Los Angeles

Recruiting

Los Angeles, California, United States, 90095

Stanford Cancer Institute

Recruiting

Palo Alto, California, United States, 94304

University of Colorado Hospital - Anschutz Cancer Pavilion(ACP)

Recruiting

Aurora, Colorado, United States, 80045

The Melanoma & Skin Cancer Institute

Recruiting

Englewood, Colorado, United States, 80113

Georgetown University Medical Center

Recruiting

Washington D.C., District of Columbia, United States, 20007

Mayo Clinic - Jacksonville FL

Recruiting

Jacksonville, Florida, United States, 32224

Sylvester Comprehensive Cancer Center

Recruiting

Miami, Florida, United States, 33136

Emory Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Northwestern Memorial Hospital

Recruiting

Chicago, Illinois, United States, 60611

University of Chicago Medical Center

Recruiting

Chicago, Illinois, United States, 60637

University of Iowa

Recruiting

Iowa City, Iowa, United States, 52242

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Mayo Clinic Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

The Ohio State University

Recruiting

Columbus, Ohio, United States, 43210

Thomas Jefferson University

Recruiting

Philadelphia, Pennsylvania, United States, 19107

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

The West Clinic, PLLC dba West Cancer Center

Recruiting

Germantown, Tennessee, United States, 38138

University of Tennessee Medical Center

Recruiting

Knoxville, Tennessee, United States, 37920

Sarah Cannon Research Institute

Recruiting

Nashville, Tennessee, United States, 37203

Vanderbilt Ingram Cancer Center (Henry-Joyce Cancer Clinic)

Recruiting

Nashville, Tennessee, United States, 37232

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

The University Of Texas Md Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

University Of Wisconsin Carbone Cancer Center - University Hospital

Recruiting

Madison, Wisconsin, United States, 53792

More Information

Sponsor

Replimune Inc.

Last update posted

Apr 2, 2026

Last verified

Mar, 2026

Keywords

  • Metastatic
  • Uveal
  • Melanoma
  • Nivolumab
  • Ipilimumab
  • Randomized
  • Immune checkpoint inhibitor-naïve
  • RP2
  • Oncolytic viruses
  • HSV-1

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Replimune Inc. on 2026-04-02.