Clinical trial NCT06581406: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Metastatic Uveal Melanoma
Keywords: Metastatic
Uveal
Melanoma
Nivolumab
Ipilimumab
Randomized
Immune checkpoint inhibitor-naïve
RP2
Oncolytic viruses
HSV-1
Lead sponsor: Replimune Inc.
Sponsor class: INDUSTRY
First posted: 2024-09-03
Enrollment: 280
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From Day 1 up to 3 years after last dose.
measure: Progression Free Survival (PFS)
timeFrame: From Day 1 up to 3 years after last dose.
Secondary outcomes:
measure: Number of patients with treatment-emergent adverse events (TEAEs)
timeFrame: From first dose up to 100 days after last dose.
measure: Overall Response Rate (ORR)
timeFrame: Every 12 weeks from Day 1 up to 3 years after last dose.
measure: Disease Control Rate (DCR)
timeFrame: Every 12 weeks from Day 1 up to 3 years after last dose.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Insisute
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Germantown
country: United States
facility: The West Clinic, PLLC dba West Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center (Henry-Joyce Cancer Clinic)
state: Tennessee
city: Houston
country: United States
facility: The University Of Texas Md Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University Of Wisconsin Carbone Cancer Center - University Hospital
state: Wisconsin
Study officials:
affiliation: Replimune Inc.
name: Rahul Marpadga, MD MPH
role: STUDY_DIRECTOR
References: