Testing a New Virus-Based Treatment Combined With Immunotherapy for Advanced Eye Melanoma

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

Replimune Inc.PHASE2 / PHASE3Recruiting
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In Plain English

This trial is testing whether a new combination of two drugs works better than a standard combination for treating uveal melanoma that has spread to other parts of your body. You haven't received immune checkpoint inhibitor therapy before (this is a specific type of cancer treatment that helps your immune system fight cancer). One group will receive RP2 (a specially engineered virus designed to attack cancer cells and wake up your immune system) plus nivolumab (a drug that removes the 'brakes' on your immune cells). The other group will receive ipilimumab (a different immune-boosting drug) plus nivolumab. Researchers want to see which combination helps patients live longer and controls their cancer better, and which one has fewer side effects. You'll be randomly assigned to one of these two groups—like a coin flip—so neither you nor the doctors know in advance which treatment you'll receive.

What This Trial Does

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 uveal melanoma who have not been treated with immune checkpoint inhibitor therapy.

Who Can Join

  • 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

Treatments

RP2 (BIOLOGICAL)

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

Ipilimumab (BIOLOGICAL)

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

Nivolumab (BIOLOGICAL)

Nivolumab: Anti-PD-1 Monoclonal antibody

Trial Sites (31)

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HonorHealth Research Insisute

Scottsdale, Arizona, United States

Justin Moser, MD

Recruiting

UC San Diego Moores Cancer Center

La Jolla, California, United States

Gregory Daniels, MD

Recruiting

The Angeles Clinic and Research Institute

Los Angeles, California, United States

Inderjit Mehmi, MD

Recruiting

University of California Los Angeles

Los Angeles, California, United States

Bartosz Chmielowski, MD

Recruiting

Stanford Cancer Institute

Palo Alto, California, United States

Allison Betof Warner, MD

Recruiting

University of Colorado Hospital - Anschutz Cancer Pavilion(ACP)

Aurora, Colorado, United States

Sapna Pradyuman Patel, MD

Recruiting

The Melanoma & Skin Cancer Institute

Englewood, Colorado, United States

Ryan Weight, DO, MS

Recruiting

Georgetown University Medical Center

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

Suthee Rapisuwon, MD

Recruiting

Mayo Clinic - Jacksonville FL

Jacksonville, Florida, United States

Roxana S. Dronca, MD

Recruiting

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Leonel Fernando Hernandez Aya, MD

Recruiting

Emory Winship Cancer Institute

Atlanta, Georgia, United States

Michael Lowe, MD

Recruiting

Northwestern Memorial Hospital

Chicago, Illinois, United States

Sunandana Chandra, MD, MS

Recruiting

University of Chicago Medical Center

Chicago, Illinois, United States

Daniel Olson, MD

Recruiting

University of Iowa

Iowa City, Iowa, United States

Asad Javed, MD

Recruiting

Massachusetts General Hospital

Boston, Massachusetts, United States

Kamaneh Montazeri, MD

Recruiting

Mayo Clinic Rochester

Rochester, Minnesota, United States

Arkadiusz Z. Dudek, MD

Recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Alexander Shoushtari, MD

Recruiting

Duke University Medical Center

Durham, North Carolina, United States

April Salama, MD

Recruiting

The Ohio State University

Columbus, Ohio, United States

Richard Wu, MD, PhD

Recruiting

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Marlana Orloff, MD

Recruiting

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Diwakar Davar, MD

Recruiting

The West Clinic, PLLC dba West Cancer Center

Germantown, Tennessee, United States

Arnel M. Pallera, MD

Recruiting

University of Tennessee Medical Center

Knoxville, Tennessee, United States

Timothy Panella, MD

Recruiting

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Meredith Ann McKean, MD, MPH

Recruiting

Vanderbilt Ingram Cancer Center (Henry-Joyce Cancer Clinic)

Nashville, Tennessee, United States

Douglas B. Johnson, MD

Recruiting

UT Southwestern Medical Center

Dallas, Texas, United States

Sanjay Chandrasekaran, MD

Recruiting

The University Of Texas Md Anderson Cancer Center

Houston, Texas, United States

Alexandra Ikeguchi, MD

Recruiting

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Natalie Miller, MD, PhD

Recruiting

University Of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Vincent Ma, MD

Recruiting

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, Merseyside, United Kingdom

Joseph Sacco

Recruiting

The Royal Marsden NHS Foundation Trust

London, United Kingdom

James Larkin

Recruiting