Metastatic Uveal MelanomaPhase 2/3NCT06581406
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
A Phase 2/3 study testing RP2, Ipilimumab and Nivolumab in people with Metastatic Uveal Melanoma, run by Replimune, Inc. at 33 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Metastatic Uveal Melanoma
- What is being tested?
- RP2, Ipilimumab and Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 33 sitesin 3 countries
- Study dates
- 17 Dec 2024to Oct 2031
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
33 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
Giuseppe Gullo, MD contact
33 sites in 3 countries
United States29 sites, 29 recruiting
- Recruiting
Emory Winship Cancer Institute
Atlanta, Georgia, 30322
Michael Lowe, MD
- Recruiting
University of Colorado Hospital - Anschutz Cancer Pavilion(ACP)
Aurora, Colorado, 80045
Sapna Pradyuman Patel, MD
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Kamaneh Montazeri, MD
- Recruiting
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Sunandana Chandra, MD, MS
- Recruiting
University of Chicago Medical Center
Chicago, Illinois, 60637
Daniel Olson, MD
- Recruiting
The Ohio State University
Columbus, Ohio, 43210
Richard Wu, MD, PhD
- Recruiting
UT Southwestern Medical Center
Dallas, Texas, 75390
Sanjay Chandrasekaran, MD
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
April Salama, MD
- Recruiting
The Melanoma & Skin Cancer Institute
Englewood, Colorado, 80113
Ryan Weight, DO, MS
- Recruiting
The West Clinic, PLLC dba West Cancer Center
Germantown, Tennessee, 38138
Arnel M. Pallera, MD
- Recruiting
The University Of Texas Md Anderson Cancer Center
Houston, Texas, 77030
Alexandra Ikeguchi, MD
- Recruiting
University of Iowa
Iowa City, Iowa, 52242
Asad Javed, MD
- Recruiting
Mayo Clinic - Jacksonville FL
Jacksonville, Florida, 32224
Roxana S. Dronca, MD
- Recruiting
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
Timothy Panella, MD
- Recruiting
UC San Diego Moores Cancer Center
La Jolla, California, 92037
Gregory Daniels, MD
- Recruiting
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
Inderjit Mehmi, MD
- Recruiting
University of California Los Angeles
Los Angeles, California, 90095
Bartosz Chmielowski, MD
- Recruiting
University Of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Vincent Ma, MD
- Recruiting
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Leonel Fernando Hernandez Aya, MD
- Recruiting
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Meredith Ann McKean, MD, MPH
- Recruiting
Vanderbilt Ingram Cancer Center (Henry-Joyce Cancer Clinic)
Nashville, Tennessee, 37232
Douglas B. Johnson, MD
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Alexander Shoushtari, MD
- Recruiting
Stanford Cancer Institute
Palo Alto, California, 94304
Allison Betof Warner, MD
- Recruiting
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Marlana Orloff, MD
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Diwakar Davar, MD
- Recruiting
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Arkadiusz Z. Dudek, MD
- Recruiting
HonorHealth Research Insisute
Scottsdale, Arizona, 85258
Justin Moser, MD
- Recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Natalie Miller, MD, PhD
- Recruiting
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Suthee Rapisuwon, MD
Australia2 sites, 2 recruiting
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Damien Kee, MD
- Recruiting
Melanoma Institute Australia
Wollstonecraft, New South Wales, 2065
Georgina Long, MD
United Kingdom2 sites, 2 recruiting
- Recruiting
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, Merseyside, L7 8YA
Joseph Sacco
- Recruiting
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
James Larkin
About this study
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
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
- Being tested
- RP2, Ipilimumab, Nivolumab
- Keywords
- Metastatic, Uveal, Melanoma, Nivolumab, Ipilimumab, Randomized, Immune checkpoint inhibitor-naïve, RP2, Oncolytic viruses, HSV-1
- Medical subject headings
- Uveal Melanoma, Neoplasm Metastasis, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP2Biological
Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation.
IpilimumabBiological
Also called Yervoy
Ipilimumab: human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody
NivolumabBiological
Also called Opdivo
Nivolumab: Anti-PD-1 Monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| Test Arm: RP2 + nivolumab | Experimental | RP2 (Oncolytic virus) and Nivolumab (programmed death receptor-1 (PD-1) inhibitor) Receives: Biological: RP2; Biological: Nivolumab |
| Control Arm (Active Comparator): ipilimumab + nivolumab | Experimental | Immune Checkpoint inhibitor combination Receives: Biological: Ipilimumab; Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS is the time from the date of randomization to death from any cause.
Measured: 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.
Measured: From Day 1 up to 3 years after last dose.
Secondary outcomes (3)
Number of patients with treatment-emergent adverse events (TEAEs)
The incidence of all TEAEs.
Measured: From first dose up to 100 days after last dose.
Overall Response Rate (ORR)
ORR is the proportion of patients with a confirmed best overall response of complete response (CR) or partial response (PR), as assessed by BICR per RECIST v1.1.
Measured: Every 12 weeks from Day 1 up to 3 years after last dose.
Disease Control Rate (DCR)
DCR is the proportion of patients with a confirmed best overall response of CR, PR, or Stable Disease (SD), as assessed by BICR per RECIST 1.1.
Measured: Every 12 weeks from Day 1 up to 3 years after last dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2024
- Study start17 Dec 2024
- Primary completionJan 2030 (estimated)
- Study completionOct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Uveal MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Replimune, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rahul Marpadga, MD MPH, Study director, Replimune, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06581406
- Sponsor's protocol ID
- RP2-202
- Status last verified
- Mar 2026
- First submitted
- 29 Aug 2024
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06581406
- Acronym / sponsor ID
- RP2-202
- Conditions
- Metastatic Uveal Melanoma
- Keywords
- Metastatic, Uveal, Melanoma, Nivolumab, Ipilimumab, Randomized, Immune checkpoint inhibitor-naïve, RP2
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Replimune, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Dec 2024 (actual)
- Primary completion
- Jan 2030 (estimated)
- Study completion
- Oct 2031 (estimated)
- First posted
- 3 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Test Arm: RP2 + nivolumab | Experimental | Biological: RP2, Biological: NivolumabRP2 (Oncolytic virus) and Nivolumab (programmed death receptor-1 (PD-1) inhibitor) |
| Control Arm (Active Comparator): ipilimumab + nivolumab | Experimental | Biological: Ipilimumab, Biological: NivolumabImmune Checkpoint inhibitor combination |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RP2Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation. | Biological | Test Arm: RP2 + nivolumab |
| IpilimumabAlso: YervoyIpilimumab: human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody | Biological | Control Arm (Active Comparator): ipilimumab + nivolumab |
| NivolumabAlso: OpdivoNivolumab: Anti-PD-1 Monoclonal antibody | Biological | Control Arm (Active Comparator): ipilimumab + nivolumab, Test Arm: RP2 + nivolumab |
Primary outcome
Overall Survival (OS)
Time frame: From Day 1 up to 3 years after last dose.
OS is the time from the date of randomization to death from any cause.
Progression Free Survival (PFS)
Time frame: From Day 1 up to 3 years after last dose.
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.
3 secondary outcomes
Number of patients with treatment-emergent adverse events (TEAEs)
Time frame: From first dose up to 100 days after last dose.
Overall Response Rate (ORR)
Time frame: Every 12 weeks from Day 1 up to 3 years after last dose.
Disease Control Rate (DCR)
Time frame: Every 12 weeks from Day 1 up to 3 years after last dose.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giuseppe Gullo, MD contact
Rahul Marpadga, MD MPH study director
Replimune, Inc.
33 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing RP2, Ipilimumab and Nivolumab in people with Metastatic Uveal Melanoma, run by Replimune, Inc. at 33 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials at Replimune (1-781-222-9570, Clinicaltrials@replimune.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: From Day 1 up to 3 years after last dose.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.