Clinical trial NCT06264180: VO and Nivolumab vs Physician's Choice in Advanced Melanoma That Progressed on Anti-PD-1 & Anti-CTLA-4 Drugs (IGNYTE-3)
Official title: Randomized, Ph3 Clinical Study Comparing Vusolimogene Oderparepvec in Combination With Nivolumab Vs Treatment of Physician's Choice in Patients With Advanced Melanoma That Progressed on Anti-PD-1 and Anti-CTLA-4 Containing Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Advanced Melanoma
Lead sponsor: Replimune Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-16
Enrollment: 400
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Key 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.

Key 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Assessed up to January 2029, approximately 55 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Assessed up to January 2029, approximately 55 months
measure: Objective Response Rate (ORR)
timeFrame: Assessed up to January 2029, approximately 55 months
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: California
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: USC Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine - Hematology/Oncology
state: California
city: Orange
country: United States
facility: UC Irvine Health, Chao Family Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Sacramento
country: United States
facility: Sutter Medical Group
state: California
city: San Francisco
country: United States
facility: San Francisco Oncology Associates
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville Brown Cancer Center
state: Kentucky
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center - Atlantic Health System
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University- Martha Morehouse Tower
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Germantown
country: United States
facility: West Cancer Center and Research Institute
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Murray
country: United States
facility: Intermountain Health
state: Utah
city: Saint George
country: United States
facility: St. George Regional Hospital
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: Replimune Inc.
name: Giuseppe Gullo, MD
role: STUDY_DIRECTOR
References: