Trial: A Randomized, Phase 2/3 Study to Invest…

Trial Details

Sponsor: Replimune Inc. (industry)

Phase: 2/3

Start date: Dec. 17, 2024

Planned enrollment: 280

Trial ID: NCT06581406

More trial details at ClinicalTrials.gov

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Goal: Compare the efficacy and safety of RP2 plus nivolumab with ipilimumab plus nivolumab in immune checkpoint inhibitor–naïve metastatic uveal melanoma.

Patients: Adults with unresectable metastatic uveal melanoma, ECOG performance status 0–1, LDH ≤2 times the upper limit of normal, and at least one measurable tumor accessible for repeated injection. Patients must agree to tumor biopsies. Key exclusions include prior checkpoint inhibitor treatment, CNS involvement, active significant herpetic infection, and autoimmune disease requiring systemic treatment.

Design: Randomized, open-label comparison of two treatment arms.

Treatments: The investigational arm receives intratumoral RP2 plus nivolumab. RP2 is an engineered oncolytic HSV-1 designed to replicate in tumors and express a fusogenic protein, GM-CSF, and an anti–CTLA-4 antibody to promote tumor destruction and antitumor immunity; nivolumab provides PD-1 blockade. In a small, nonrandomized phase 1 uveal melanoma subgroup, 5 of 15 evaluable patients responded, but this does not establish comparative benefit. The comparator is ipilimumab plus nivolumab, combining CTLA-4 and PD-1 blockade.

Outcomes: Primary endpoints are overall survival and progression-free survival, with progression assessed by blinded independent central review using RECIST 1.1. Secondary endpoints include treatment-emergent adverse events, confirmed objective response rate, and disease control rate; tumor responses are assessed every 12 weeks.

Burden on patient: Moderate to high, particularly in the RP2 arm: patients need repeated intratumoral injections and tumor biopsies, in addition to treatment visits and imaging approximately every 12 weeks. Injection access and biopsy requirements may add travel and procedural burden beyond routine systemic therapy; the exact visit and biopsy frequency is not specified.

Last updated: Sep 2026

Eligibility

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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.

Trial Details

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Investigational Drug AI Analysis

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Overview

Mechanism of action

Efficacy

Safety

Further reading

TrialFetch AI Analysis

Eligibility

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Sites (33)

Melanoma Institute Australia

Peter MacCallum Cancer Centre

The Royal Marsden NHS Foundation Trust

The Clatterbridge Cancer Centre NHS Foundation Trust

HonorHealth Research Insisute

Stanford Cancer Institute

The Angeles Clinic and Research Institute

UC San Diego Moores Cancer Center

University of California Los Angeles

The Melanoma & Skin Cancer Institute

University of Colorado Hospital - Anschutz Cancer Pavilion(ACP)

Georgetown University Medical Center

Mayo Clinic - Jacksonville FL

Sylvester Comprehensive Cancer Center

Emory Winship Cancer Institute

Northwestern Memorial Hospital

University of Chicago Medical Center

University of Iowa

Massachusetts General Hospital

Mayo Clinic Rochester

Memorial Sloan Kettering Cancer Center

Duke University Medical Center

The Ohio State University

Thomas Jefferson University

UPMC Hillman Cancer Center

Sarah Cannon Research Institute

The West Clinic, PLLC dba West Cancer Center

University of Tennessee Medical Center

Vanderbilt Ingram Cancer Center (Henry-Joyce Cancer Clinic)

The University Of Texas Md Anderson Cancer Center

UT Southwestern Medical Center

Fred Hutchinson Cancer Center

University Of Wisconsin Carbone Cancer Center - University Hospital