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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 · Replimune, Inc.
In plain English
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Official title
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
About this study
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.
Eligibility criteria
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 target: 280 participants
Allocation: randomized
Masking: none
Age groups: child, adult, older_adult
Timeline
Starts: 2024-12-17
Estimated completion: 2031-10
Last updated: 2026-04-02
Interventions
Biological: RP2Biological: IpilimumabBiological: Nivolumab
Primary outcomes
- • Overall Survival (OS) (From Day 1 up to 3 years after last dose.)
- • Progression Free Survival (PFS) (From Day 1 up to 3 years after last dose.)
Sponsor
Replimune, Inc. · industry
Contacts & investigators
ContactClinical Trials at Replimune · contact · Clinicaltrials@replimune.com · 1-781-222-9570
ContactGiuseppe Gullo, MD · contact
InvestigatorRahul Marpadga, MD MPH · study_director, Replimune, Inc.
All locations (33)
HonorHealth Research InsisuteRecruiting
Scottsdale, Arizona, United States
UC San Diego Moores Cancer CenterRecruiting
La Jolla, California, United States
The Angeles Clinic and Research InstituteRecruiting
Los Angeles, California, United States
University of California Los AngelesRecruiting
Los Angeles, California, United States
Stanford Cancer InstituteRecruiting
Palo Alto, California, United States
University of Colorado Hospital - Anschutz Cancer Pavilion(ACP)Recruiting
Aurora, Colorado, United States
The Melanoma & Skin Cancer InstituteRecruiting
Englewood, Colorado, United States
Georgetown University Medical CenterRecruiting
Washington D.C., District of Columbia, United States
Mayo Clinic - Jacksonville FLRecruiting
Jacksonville, Florida, United States
Sylvester Comprehensive Cancer CenterRecruiting
Miami, Florida, United States
Emory Winship Cancer InstituteRecruiting
Atlanta, Georgia, United States
Northwestern Memorial HospitalRecruiting
Chicago, Illinois, United States
University of Chicago Medical CenterRecruiting
Chicago, Illinois, United States
University of IowaRecruiting
Iowa City, Iowa, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Mayo Clinic RochesterRecruiting
Rochester, Minnesota, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
Duke University Medical CenterRecruiting
Durham, North Carolina, United States
The Ohio State UniversityRecruiting
Columbus, Ohio, United States
Thomas Jefferson UniversityRecruiting
Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer CenterRecruiting
Pittsburgh, Pennsylvania, United States
The West Clinic, PLLC dba West Cancer CenterRecruiting
Germantown, Tennessee, United States
University of Tennessee Medical CenterRecruiting
Knoxville, Tennessee, United States
Sarah Cannon Research InstituteRecruiting
Nashville, Tennessee, United States
Vanderbilt Ingram Cancer Center (Henry-Joyce Cancer Clinic)Recruiting
Nashville, Tennessee, United States
UT Southwestern Medical CenterRecruiting
Dallas, Texas, United States
The University Of Texas Md Anderson Cancer CenterRecruiting
Houston, Texas, United States
Fred Hutchinson Cancer CenterRecruiting
Seattle, Washington, United States
University Of Wisconsin Carbone Cancer Center - University HospitalRecruiting
Madison, Wisconsin, United States
Melanoma Institute AustraliaRecruiting
Wollstonecraft, New South Wales, Australia
Peter MacCallum Cancer CentreRecruiting
Melbourne, Victoria, Australia
The Clatterbridge Cancer Centre NHS Foundation TrustRecruiting
Liverpool, Merseyside, United Kingdom
The Royal Marsden NHS Foundation TrustRecruiting
London, United Kingdom