VO and Nivolumab vs Physician's Choice in Advanced Melanoma That Progressed on Anti-PD-1 & Anti-CTLA-4 Drugs (IGNYTE-3)
Purpose
This is a randomized, controlled, multicenter, open-label Phase 3 clinical study comparing VO in combination with nivolumab versus Physician's Choice treatment for patients with unresectable Stage IIIb-IV cutaneous melanoma whose disease progressed on an anti PD-1 and an anti-CTLA-4 containing regimen (administered either as a combination regimen or in sequence) or who are not candidates for treatment with an anti-CTLA-4 therapy.
Condition
- Advanced Melanoma
Eligibility
- Eligible Ages
- Over 12 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Male or female who is 12 years of age or older at the time of signed informed consent. - Patients with histologically or cytologically confirmed unresectable or metastatic Stage IIIb through IV/M1a through M1d cutaneous melanoma. - Confirmed disease progression (PD) on an approved anti-PD-1 and an anti-CTLA-4 treatment, administered either as a combination regimen (eg, nivolumab + ipilimumab) or in sequence. 1. Treatment with prior anti-PD-1 therapy must have continued for a minimum of 8 weeks 2. Patients who in the physician's judgement are not candidates for treatment with an anti-CTLA-4 antibody are eligible - Has documented BRAF V600 mutation status. Patients with BRAF mutation should have received prior BRAF-directed therapy (with or without a MEK inhibitor) prior to enrollment in the study, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition or prior toxicity. - Has at least 1 measurable and injectable tumor of ≥1 cm in longest diameter (or shortest diameter for lymph nodes). - Has adequate hematologic function. - Has adequate hepatic function. - Has adequate renal function. - Prothrombin time (PT) ≤1.5 × ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5 × ULN - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1 for patients 18 years and older or a Lansky performance score (PSc) ≥80 for patients 12 to 17 years of age. - Life expectancy of at least 3 months. - Female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements during the treatment period and for at least 6 months after the last dose of study treatment. - Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test within 72 hours before the first dose of study treatment.
Exclusion Criteria
- Primary mucosal or uveal melanoma. - More than 2 lines of systemic therapy for advanced melanoma. - Known acute or chronic hepatitis. - Known human immunodeficiency virus (HIV) infection. - Active significant herpetic infections or prior complications of HSV-1 infection. - Had systemic infection requiring IV antibiotics or other serious active infection requiring antimicrobial, antiviral, or antifungal treatment within 14 days prior to dosing. - With active significant herpetic infections or prior complications of HSV-1 infection. - Evidence of spinal cord compression or at high risk of spinal cord compression. - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis at time of screening. - Serum lactate dehydrogenase (LDH) >2 × ULN. - Major surgery ≤2 weeks prior to starting study drug. - Prior malignancy active within the previous 3 years, except for locally curable cancers that have apparently been cured - History of significant cardiac disease including myocarditis or congestive heart. - History of life-threatening toxicity related to prior immune. - Active, known, or suspected autoimmune disease requiring systemic treatment. - History of (noninfectious) pneumonitis that required steroids or has current pneumonitis. - Prior oncolytic virus or other therapy given by intratumoral administration. - Requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir). - Has received a live vaccine within 28 days prior to the first dose of study treatment. - Systemic anticancer therapies within 5 half-lives or 4 weeks of the first dose, whichever is shorter. - 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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental VO + nivolumab |
|
|
|
Active Comparator Physicians Choice |
Choosing from 1 of the following (to be consistent with approved label and/or applicable local clinical guidelines): - Nivolumab + relatlimab (as Opdualag) - Anti-PD-1 monotherapy (nivolumab or pembrolizumab) - Single-agent chemotherapy (dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel) |
|
Recruiting Locations
University of Kansas Cancer Center
Westwood, Kansas 66205
Westwood, Kansas 66205
More Details
- Status
- Recruiting
- Sponsor
- Replimune Inc.