Metastatic Uveal Melanoma
Conditions
Keywords
Metastatic, Uveal, Melanoma, Nivolumab, Ipilimumab, Randomized, Immune checkpoint inhibitor-naïve, RP2, Oncolytic viruses, HSV-1
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.
Interventions
BIOLOGICALRP2
Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation.
BIOLOGICALIpilimumab
Ipilimumab: human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody
BIOLOGICALNivolumab
Nivolumab: Anti-PD-1 Monoclonal antibody
Sponsors
Replimune Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with treatment-emergent adverse events (TEAEs) | From first dose up to 100 days after last dose. | The incidence of all TEAEs. |
| Overall Response Rate (ORR) | Every 12 weeks from Day 1 up to 3 years after last dose. | 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. |
| Disease Control Rate (DCR) | Every 12 weeks from Day 1 up to 3 years after last dose. | 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. |
Countries
Australia, United Kingdom, United States
Contacts
CONTACTClinical Trials at Replimune
CONTACTGiuseppe Gullo, MD
STUDY_DIRECTORRahul Marpadga, MD MPH
Replimune Inc.
Outcome results
None listed