VO and Nivolumab vs Physician's Choice in Advanced Melanoma That Progressed on Anti-PD-1 & Anti-CTLA-4 Drugs [IGNYTE-3]
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 [IGNYTE-3]
1 other identifier
interventional
400
6 countries
73
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2024
Longer than P75 for phase_3
73 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 29, 2024
CompletedFirst Posted
Study publicly available on registry
February 16, 2024
CompletedStudy Start
First participant enrolled
July 11, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2034
March 13, 2026
March 1, 2026
4.5 years
January 29, 2024
March 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
Time from the date of randomization to death due to any cause
Assessed up to January 2029, approximately 55 months
Secondary Outcomes (2)
Progression Free Survival (PFS)
Assessed up to January 2029, approximately 55 months
Objective Response Rate (ORR)
Assessed up to January 2029, approximately 55 months
Study Arms (2)
VO + nivolumab
EXPERIMENTALPhysicians Choice
ACTIVE COMPARATORChoosing 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)
Interventions
Anti-PD-1 Monoclonal Antibody
Nivolumab: Anti-PD-1 Monoclonal antibody. Relatlimab: A lymphocyte activation gene-3 (LAG-3) blocking antibody.
A programmed death receptor-1 (PD-1)-blocking antibody indicated.
Dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel.
Genetically modified Herpes Simplex Type 1 Virus.
Eligibility Criteria
You may qualify if:
- I 1. Male or female who is 12 years of age or older at the time of signed informed consent.
- I 2. Patients with histologically or cytologically confirmed unresectable or metastatic Stage IIIb through IV/M1a through M1d cutaneous melanoma, as per AJCC staging system, 8th edition).
- I 3. Confirmed disease progression (PD) on an anti-PD-1 antibody treatment and an anti-CTLA-4 antibody treatment, administered as either a combination regimen (eg, nivolumab + ipilimumab) or in sequence.
- Treatment with prior anti-PD-1 therapy must have continued for a minimum of 8 weeks (note: treatment with prior pembrolizumab therapy when administered every 6 weeks must have continued for a minimum of 12 weeks \[ie, 2 treatment cycles\]). Any number of doses of prior anti-CTLA-4 therapy may have been administered in combination with an anti-PD-1. The anti-PD-1-containing therapy must be the immediate prior line of treatment before randomization (for patients with BRAF mutation, see I 4).
- Patients who in the physician's judgement are not candidates for treatment with an anti-CTLA-4 antibody (eg, due to documented clinically significant comorbidities or history of immune-related adverse events) are eligible for the study if they have confirmed PD on an anti-PD-1 antibody (including unresectable disease relapse during adjuvant therapy or \< 6 months from completion of adjuvant therapy).
- Disease progression must have been confirmed and documented using clinical or radiological assessment by 2 assessments at least 4 weeks apart while being treated with an anti-PD-1 antibody and an anti-CTLA-4 antibody. Radiological confirmation of PD can occur during the Screening period for this study. Treatment with prior anti-PD-1 therapy must have continued from the time of initial tumor progression until confirmation of PD (ie, such that no doses of anti-PD-1 therapy were missed).
- Note: If radiographic progression at the initial scan where PD was documented is accompanied by clear clinical progression, defined as a decline in performance status directly attributed to disease or increased disease-related symptoms, anti-PD-1 therapy does not need to continue. For patients with documented PD while on adjuvant therapy with an anti-PD-1 therapy, a confirmatory biopsy can be used in place of a confirmatory scan.
- I 4. Has documented BRAF V600 mutation status or must consent to BRAF V600 mutation testing per local institutional standards during the Screening period. Patients with BRAF mutation should have received prior BRAF-directed therapy (with or without a MEK inhibitor) prior to randomization, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition or prior toxicity.
- Note: Prior exposure to BRAF-directed therapy (with or without a MEK inhibitor) includes treatment in the adjuvant setting. One line of BRAF-directed therapy (with or without a MEK inhibitor) can be the most recent systemic treatment administered before randomization.
- I 5. Has least 1 measurable tumor of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes) and injectable lesion(s) of at least 1 cm in longest diameter.
- I 6. Has adequate hematologic function, including:
- White blood cell (WBC) count ≥ 2.0 × 109/L
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
- Platelet count ≥ 75 × 109/L
- Hemoglobin ≥ 8 g/dL (without packed red blood cell \[RBC\] transfusion within 2 weeks of dosing)
- +9 more criteria
You may not qualify if:
- E 1. Primary mucosal or uveal melanoma. E 2. More than 2 lines of systemic therapy for advanced melanoma. Note: One additional line of anti-PD-1 therapy in the adjuvant or neoadjuvant setting is allowed if the patient was free of treatment and of PD for at least 6 months and subsequently had confirmed PD on an anti-PD-1 and an anti-CTLA-4 antibody therapy administered in the advanced setting.
- E 3. Known acute or chronic hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known acute or chronic hepatitis C virus (defined as HCV RNA \[qualitative\] is detected).
- Note: Patients who have been effectively treated are eligible for randomization. Patients must be negative for HBsAg and HCV RNA.
- E 4. Known human immunodeficiency virus (HIV) infection. Note: Testing for HIV is not required unless mandated by local health authority or clinically indicated.
- E 5. Active significant herpetic infections or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis) or requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
- Note: Patients with sporadic cold sores may be randomized if no active cold sores are present at the time of first dose of study treatment.
- E 6. Had systemic infection requiring IV antibiotics or other serious active infection requiring antimicrobial, antiviral, or antifungal treatment within 14 days prior to the first dose.
- E 7. Evidence of spinal cord compression or at high risk of spinal cord compression.
- E 8. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis at time of screening. Patients with known central nervous system metastases are eligible if they have received standard-of-care therapy for central nervous system disease (such as stereotactic radiosurgery or radical surgical resection followed by radiotherapy) and have evidence of disease stability on 2 subsequent scans performed at least at a 4-week interval.
- E 9. Serum lactate dehydrogenase (LDH) \> 2 × ULN. E 10. Major surgery ≤ 2 weeks prior to starting study treatment. Note: Patients must have recovered adequately from all acute complications of all previous procedures prior to randomization.
- E 11. Prior malignancy active within the previous 3 years, except for locally curable cancers that have apparently been cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ (without invasive component) of the prostate, cervix, or breast.
- E 12. History of significant cardiac disease including myocarditis or congestive heart failure (defined as New York Heart Association Functional Classification III or IV), or unstable angina, serious uncontrolled cardiac arrhythmia, cerebral vascular accident, or myocardial infarction within 6 months from first dose of VO.
- E 13. History of life-threatening toxicity related to prior immune therapy except those that are unlikely to recur with standard countermeasures (eg, hormone replacement after adrenal crisis).
- E 14. History or evidence of psychiatric, substance abuse (including IV substance abuse), or any other clinically significant disorder, condition, or disease (with the exception of those described above) that, in the opinion of the Investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion.
- E 15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Replimune Inc.lead
Study Sites (73)
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92037, United States
The Angeles Clinic and Research Institute
Los Angeles, California, 90025, United States
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UCLA Department of Medicine - Hematology/Oncology
Los Angeles, California, 90095, United States
UC Irvine Health, Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Stanford Cancer Institute
Palo Alto, California, 94304, United States
Sutter Medical Group
Sacramento, California, 95816, United States
San Francisco Oncology Associates
San Francisco, California, 94115, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94143, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, 80045, United States
The Melanoma and Skin Cancer Institute
Englewood, Colorado, 80113, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
Memorial Cancer Institute at Memorial Regional Hospital
Hollywood, Florida, 33021, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Advocate Lutheran General Hospital
Park Ridge, Illinois, 60068, United States
University of Iowa
Iowa City, Iowa, 52242, United States
University of Kansas Cancer Center
Westwood, Kansas, 66205, United States
University of Louisville Brown Cancer Center
Louisville, Kentucky, 40202, United States
Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)
Detroit, Michigan, 48202, United States
Corewell Health
Grand Rapids, Michigan, 49503, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Dartmouth Hitchcock Cancer Center
Lebanon, New Hampshire, 03756, United States
MD Anderson Cancer Center at Cooper
Camden, New Jersey, 08103, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Morristown Medical Center - Atlantic Health System
Morristown, New Jersey, 07960, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Northwell Health, R.J. Zuckerberg Cancer Center
Lake Success, New York, 11042, United States
Stony Brook University Cancer Center
Stony Brook, New York, 11794, United States
Montefiore Medical Center
The Bronx, New York, 10461, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514, United States
Duke Cancer Center
Durham, North Carolina, 27710, United States
The Ohio State University- Martha Morehouse Tower
Columbus, Ohio, 43210, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
UPMC
Pittsburgh, Pennsylvania, 15232, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
West Cancer Center and Research Institute
Germantown, Tennessee, 38138, United States
University of Tennessee
Knoxville, Tennessee, 37920, United States
Texas Oncology
Dallas, Texas, 75246, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Intermountain Health
Murray, Utah, 84107, United States
Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
St. George Regional Hospital
St. George, Utah, 84790, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
West Virginia University
Morgantown, West Virginia, 26506, United States
CHU de Lille
Lille, 59000, France
Hopital de La Timone
Marseille, 13005, France
CHU Nice
Nice, 06200, France
Hôpital Saint Louis - AP-HP
Paris, 75010, France
Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
Pierre-Bénite, 69495, France
Institut Gustave Roussy
Villejuif, 94800, France
Charité - Universitätsmedizin Berlin
Berlin, 10117, Germany
Helios Klinik
Erfurt, 99089, Germany
Universitätsklinikum Essen
Essen, 45147, Germany
Universitätsklinikum Medical Center
Hamburg, 20246, Germany
Universitätsklinikum Hospital Heidelberg
Heidelberg, 69120, Germany
University of Kiel
Kiel, 24105, Germany
Universitatsklinikum Mainz Hautklinik und Poliklinik
Mainz, 55131, Germany
Universitätsklinikum of Tübingen
Tübingen, 72076, Germany
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-214, Poland
Maria Sklodowska-Curie National Research Institute of Oncology
Warsaw, 02-781, Poland
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
El Palmar, 30120, Spain
Clinica Universidad de Navarra - Madrid
Madrid, 28027, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Clinica Universidad de Navarra - Pamplona
Pamplona, 31008, Spain
Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, L7 8YA, United Kingdom
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ, United Kingdom
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Giuseppe Gullo, MD
Replimune Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 29, 2024
First Posted
February 16, 2024
Study Start
July 11, 2024
Primary Completion (Estimated)
January 1, 2029
Study Completion (Estimated)
August 31, 2034
Last Updated
March 13, 2026
Record last verified: 2026-03