VO and Nivolumab vs Physician's Choice in Advanced Melanoma That Progressed on Anti-PD-1 & Anti-CTLA-4 Drugs [IGNYTE-3]
NCT ID: NCT06264180
Last Updated: 2025-12-23
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
400 participants
INTERVENTIONAL
2024-07-11
2034-08-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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VO + nivolumab
Vusolimogene Oderparepvec
Genetically modified Herpes Simplex Type 1 Virus.
Nivolumab
Anti-PD-1 Monoclonal Antibody
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)
Nivolumab
Anti-PD-1 Monoclonal Antibody
Nivolumab + Relatlimab
Nivolumab: Anti-PD-1 Monoclonal antibody. Relatlimab: A lymphocyte activation gene-3 (LAG-3) blocking antibody.
Pembrolizumab
A programmed death receptor-1 (PD-1)-blocking antibody indicated.
Single-agent chemotherapy
Dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel.
Interventions
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Vusolimogene Oderparepvec
Genetically modified Herpes Simplex Type 1 Virus.
Nivolumab
Anti-PD-1 Monoclonal Antibody
Nivolumab + Relatlimab
Nivolumab: Anti-PD-1 Monoclonal antibody. Relatlimab: A lymphocyte activation gene-3 (LAG-3) blocking antibody.
Pembrolizumab
A programmed death receptor-1 (PD-1)-blocking antibody indicated.
Single-agent chemotherapy
Dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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.
1. 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).
2. 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).
3. 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:
1. White blood cell (WBC) count ≥ 2.0 × 109/L
2. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
3. Platelet count ≥ 75 × 109/L
4. Hemoglobin ≥ 8 g/dL (without packed red blood cell \[RBC\] transfusion within 2 weeks of dosing)
I 7. Has adequate hepatic function, including:
1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN; \< 2.0 × ULN for patients with known Gilbert syndrome or liver metastases)
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × ULN (or ≤ 5.0 × ULN, if liver metastases are present)
3. Alkaline phosphatase (ALP) ≤ 2.5 × ULN (or ≤ 5.0 × ULN, if liver or bone metastases are present) I 8. Has adequate renal function, defined as serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 3 0 mL/minute/1.73 m2 (measured using Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula).
I 9. 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. Note: Patients who are on chronic anticoagulant therapy may be randomized if the target INR is ≤ 2.5. For patients requiring deep injection of VO, the INR must be \<1.5 at the time of injection.
I 10. ECOG performance status (PS) 0 to 1 for patients 18 and older or a Lansky PS ≥ 80 for patients 12 to 17 years of age.
I 11. Life expectancy of at least 3 months. I 12. 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 any study treatment.
I 13. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units or β hCG within 7 days before the first dose of study treatment.
I 14. Capable of giving signed informed consent which includes willingness to comply with the requirements and restrictions listed in the informed consent form (ICF)
Exclusion Criteria
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.
E 16. Active, known, or suspected autoimmune disease requiring systemic treatment.
E 17. History of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
E 18. Prior oncolytic virus therapy or other therapy given by intratumoral administration.
E 19. Requires chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
E 20. Has received a live vaccine within 28 days prior to the first dose of study treatment.
E 21. Systemic anticancer therapies within 5 half-lives or 4 weeks of the first dose, whichever is shorter.
E 22. Is currently participating in or has participated in a study of an investigational agent within 4 weeks prior to the first dose of study treatment.
E 23. Has received prior radiotherapy within 2 weeks of start of study treatment or has not recovered from radiotherapy.
E 24. Conditions requiring treatment with immunosuppressive doses (\> 10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy 14 days before randomization.
Note: Patients who require a brief course (≤ 7 days) or corticosteroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded. Physiologic replacement doses of systemic corticosteroids are permitted, only if the dose does not exceed 10 mg/day prednisone equivalent.
E 25. History of allergy or sensitivity to study drug components (VO, nivolumab, pembrolizumab, or relatlimab) or to cisplatin or carboplatin or paclitaxel (dependent on cohort) or prior monoclonal antibody treatment.
E 26. Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment.
E 27. Is a person who is deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
12 Years
ALL
No
Sponsors
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Replimune Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Giuseppe Gullo, MD
Role: STUDY_DIRECTOR
Replimune Inc.
Locations
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Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
The Angeles Clinic and Research Institute
Los Angeles, California, United States
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States
UCLA Department of Medicine - Hematology/Oncology
Los Angeles, California, United States
UC Irvine Health, Chao Family Comprehensive Cancer Center
Orange, California, United States
Stanford Cancer Institute
Palo Alto, California, United States
Sutter Medical Group
Sacramento, California, United States
San Francisco Oncology Associates
San Francisco, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, United States
The Melanoma and Skin Cancer Institute
Englewood, Colorado, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States
Memorial Cancer Institute at Memorial Regional Hospital
Hollywood, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
Advocate Lutheran General Hospital
Park Ridge, Illinois, United States
University of Iowa
Iowa City, Iowa, United States
University of Kansas Cancer Center
Westwood, Kansas, United States
University of Louisville Brown Cancer Center
Louisville, Kentucky, United States
Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)
Detroit, Michigan, United States
Corewell Health
Grand Rapids, Michigan, United States
University of Minnesota
Minneapolis, Minnesota, United States
Dartmouth Hitchcock Cancer Center
Lebanon, New Hampshire, United States
MD Anderson Cancer Center at Cooper
Camden, New Jersey, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Morristown Medical Center - Atlantic Health System
Morristown, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Northwell Health, R.J. Zuckerberg Cancer Center
Lake Success, New York, United States
Stony Brook University Cancer Center
Stony Brook, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Duke Cancer Center
Durham, North Carolina, United States
The Ohio State University- Martha Morehouse Tower
Columbus, Ohio, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
UPMC
Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
Providence, Rhode Island, United States
West Cancer Center and Research Institute
Germantown, Tennessee, United States
University of Tennessee
Knoxville, Tennessee, United States
Texas Oncology
Dallas, Texas, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Intermountain Health
Murray, Utah, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
St. George Regional Hospital
St. George, Utah, United States
University of Vermont Medical Center
Burlington, Vermont, United States
West Virginia University
Morgantown, West Virginia, United States
Hôpital Saint Louis - AP-HP
Paris, , France
Institut Gustave Roussy
Villejuif, , France
Charité - Universitätsmedizin Berlin
Berlin, , Germany
Helios Klinik
Erfurt, , Germany
Universitätsklinikum Essen
Essen, , Germany
Universitätsklinikum Medical Center
Hamburg, , Germany
Universitätsklinikum Hospital Heidelberg
Heidelberg, , Germany
Universitätsklinikum of Tübingen
Tübingen, , Germany
Uniwersyteckie Centrum Kliniczne
Gdansk, , Poland
Maria Sklodowska-Curie National Research Institute of Oncology
Warsaw, , Poland
Hospital Clínico Universitario Virgen de la Arrixaca
El Palmar, , Spain
Clinica Universidad de Navarra - Madrid
Madrid, , Spain
Clinica Universidad de Navarra - Pamplona
Pamplona, , Spain
The Royal Marsden NHS Foundation Trust
London, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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Principal Investigator Amna Sher, MD
Role: primary
Other Identifiers
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RP1-104
Identifier Type: -
Identifier Source: org_study_id