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

NCT06581406 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: RP2-202
• Study Type: interventional
• Target: 280
• Locations: 3 countries
• Sites: 33

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  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)

  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 Outcomes (3)

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

  From first dose up to 100 days after last dose.

• Overall Response Rate (ORR)

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

• Disease Control Rate (DCR)

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

Study Arms (2)

Test Arm: RP2 + nivolumab

EXPERIMENTAL

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

Biological: RP2; Biological: Nivolumab

Control Arm (Active Comparator): ipilimumab + nivolumab

EXPERIMENTAL

Immune Checkpoint inhibitor combination

Biological: Ipilimumab; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

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

Also known as: Yervoy

Control Arm (Active Comparator): ipilimumab + nivolumab

Nivolumab BIOLOGICAL

Nivolumab: Anti-PD-1 Monoclonal antibody

Also known as: Opdivo

Control Arm (Active Comparator): ipilimumab + nivolumab; Test Arm: RP2 + nivolumab

RP2 BIOLOGICAL

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

Test Arm: RP2 + nivolumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Replimune Inc.: lead

Study Sites (33)

HonorHealth Research Insisute

Scottsdale, Arizona, 85258, United States

RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92037, United States

RECRUITING

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

RECRUITING

University of California Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Stanford Cancer Institute

Palo Alto, California, 94304, United States

RECRUITING

University of Colorado Hospital - Anschutz Cancer Pavilion(ACP)

Aurora, Colorado, 80045, United States

RECRUITING

The Melanoma & Skin Cancer Institute

Englewood, Colorado, 80113, United States

RECRUITING

Georgetown University Medical Center

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

RECRUITING

Mayo Clinic - Jacksonville FL

Jacksonville, Florida, 32224, United States

RECRUITING

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

The West Clinic, PLLC dba West Cancer Center

Germantown, Tennessee, 38138, United States

RECRUITING

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt Ingram Cancer Center (Henry-Joyce Cancer Clinic)

Nashville, Tennessee, 37232, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

The University Of Texas Md Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

University Of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

RECRUITING

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, Merseyside, L7 8YA, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Uveal Melanoma; Neoplasm Metastasis; Melanoma

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue 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

• Rahul Marpadga, MD MPH

  Replimune Inc.

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials at Replimune

CONTACT

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

Giuseppe Gullo, MD

CONTACT

Study Design

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

Model Details: The study will consist of 3 periods: Screening, Treatment, and Follow-up. * 28-day Screening Period * Treatment Period: Tumor measurements will be assessed every 12 weeks (Q12W) * Safety Follow-Up - up to 100 days after the last dose of study drug. * Efficacy Follow-Up,Tumor measurements by serial radiographic imaging Q12W * Survival Follow-Up, survival information will be collected every 3 months for a minimum of 3 years

Study Record Dates

• First Submitted: August 29, 2024
• First Posted: September 3, 2024
• Study Start: December 17, 2024
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): October 1, 2031
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

US (29); GB (2); AU (2)