Genetically modified virus takes on tough melanoma

NCT ID NCT06264180

Disease control Sponsor: Replimune, Inc. Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Jul 16, 2026 · Updated 3 times

Summary

This Phase 3 trial tests whether a genetically modified herpes virus (vusolimogene oderparepvec) combined with the immunotherapy drug nivolumab can help people with advanced melanoma that has stopped responding to prior treatments. About 400 participants will receive either the virus-immunotherapy combo or a standard treatment chosen by their doctor. The main goal is to see if the combination helps people live longer.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Vusolimogene oderparepvec (a genetically modified herpes virus) combined with nivolumab (an immunotherapy drug)
What this could lead to: If successful, this combination could offer a new treatment option for people with advanced melanoma that no longer responds to standard immunotherapies.
What could go wrong: This is a large Phase 3 trial, but the virus-based therapy is still experimental. It may not improve survival or could cause side effects like flu-like symptoms or injection-site reactions.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

About 400 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jul 2024

Expected to finish

Mar 2031

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

12 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Key Inclusion Criteria: 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. 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) Key Exclusion Criteria: 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. 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.

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Conditions

The condition(s) this trial relates to.

cutaneous melanoma melanoma metastatic melanoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Advanced melanoma

How to take part

Only the study team decides who joins. These are the ways to reach them.

The places running it

75 sites in 7 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

Advocate Lutheran General Hospital
WITHDRAWN

Park Ridge, Illinois, 60068, United States
Banner MD Anderson Cancer Center
RECRUITING

Gilbert, Arizona, 85234, United States
Baptist MD Anderson Cancer Center
RECRUITING

Jacksonville, Florida, 32207, United States
CHU Nice
RECRUITING

Nice, 06200, France
CHU de Bordeaux, Hôpital Saint-André
RECRUITING

Bordeaux, 33075, France
CHU de Lille
RECRUITING

Lille, 59000, France
Charité - Universitätsmedizin Berlin
RECRUITING

Berlin, 10117, Germany
Clatterbridge Cancer Centre NHS Foundation Trust
RECRUITING

Liverpool, L7 8YA, United Kingdom
Clinica Universidad de Navarra - Madrid
RECRUITING

Madrid, 28027, Spain
Clinica Universidad de Navarra - Pamplona
RECRUITING

Pamplona, 31008, Spain
Corewell Health
RECRUITING

Grand Rapids, Michigan, 49503, United States
Dartmouth Hitchcock Cancer Center
RECRUITING

Lebanon, New Hampshire, 03756, United States
Duke Cancer Center
RECRUITING

Durham, North Carolina, 27710, United States
Fox Chase Cancer Center
RECRUITING

Philadelphia, Pennsylvania, 19111, United States
Guy's & St. Thomas' NHS Foundation Trust
RECRUITING

London, SE1 9RT, United Kingdom
Hackensack University Medical Center
RECRUITING

Hackensack, New Jersey, 07601, United States
Helios Klinik
RECRUITING

Erfurt, 99089, Germany
Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)
WITHDRAWN

Detroit, Michigan, 48202, United States
Hopital de La Timone
RECRUITING

Marseille, 13005, France
Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
RECRUITING

Pierre-Bénite, 69495, France
Hospital Clinic de Barcelona
RECRUITING

Barcelona, 08036, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
RECRUITING

El Palmar, 30120, Spain
Hospital Universitari Vall d'Hebron
RECRUITING

Barcelona, 08035, Spain
Hospital Universitario 12 de Octubre
RECRUITING

Madrid, 28041, Spain
Huntsman Cancer Institute
RECRUITING

Salt Lake City, Utah, 84112, United States
Hôpital Saint Louis - AP-HP
RECRUITING

Paris, 75010, France
Institut Gustave Roussy
RECRUITING

Villejuif, 94800, France
Intermountain Health
RECRUITING

Murray, Utah, 84107, United States
LMU München - Klinik and Poliklinik für Dermatologie und Allergologie, Dermatoonkologie
RECRUITING

München, 80337, Germany
MD Anderson Cancer Center at Cooper
WITHDRAWN

Camden, New Jersey, 08103, United States
Maria Sklodowska-Curie National Research Institute of Oncology
RECRUITING

Warsaw, 02-781, Poland
MedStar Washington Hospital Center
RECRUITING

Washington D.C., District of Columbia, 20010, United States
Memorial Cancer Institute at Memorial Regional Hospital
RECRUITING

Hollywood, Florida, 33021, United States
Moffitt Cancer Center
RECRUITING

Tampa, Florida, 33612, United States
Montefiore Medical Center
RECRUITING

The Bronx, New York, 10461, United States
Morristown Medical Center - Atlantic Health System
RECRUITING

Morristown, New Jersey, 07960, United States
National and Kapodistrian University of Athens, General Hospital of Athens "Laiko"
RECRUITING

Athens, 11527, Greece
Northwell Health, R.J. Zuckerberg Cancer Center
RECRUITING

Lake Success, New York, 11042, United States
Northwestern Memorial Hospital
RECRUITING

Chicago, Illinois, 60611, United States
Rhode Island Hospital
RECRUITING

Providence, Rhode Island, 02903, United States
Roswell Park Cancer Institute
RECRUITING

Buffalo, New York, 14263, United States
Royal Free London NHS Foundation Trust - Royal Free Hospital
RECRUITING

London, NW3 2QG, United Kingdom
San Francisco Oncology Associates
RECRUITING

San Francisco, California, 94115, United States
St. George Regional Hospital
WITHDRAWN

St. George, Utah, 84790, United States
Stanford Cancer Institute
RECRUITING

Palo Alto, California, 94304, United States
Stony Brook University Cancer Center
WITHDRAWN

Stony Brook, New York, 11794, United States
Sutter Medical Group
WITHDRAWN

Sacramento, California, 95816, United States
Texas Oncology
RECRUITING

Dallas, Texas, 75246, United States
The Angeles Clinic and Research Institute
RECRUITING

Los Angeles, California, 90025, United States
The Christie NHS Foundation Trust
RECRUITING

Manchester, M20 4BX, United Kingdom
The Melanoma and Skin Cancer Institute
RECRUITING

Englewood, Colorado, 80113, United States
The Ohio State University- Martha Morehouse Tower
RECRUITING

Columbus, Ohio, 43210, United States
The Royal Marsden NHS Foundation Trust
RECRUITING

London, SW3 6JJ, United Kingdom
The University of Texas MD Anderson Cancer Center
RECRUITING

Houston, Texas, 77030, United States
Thomas Jefferson University
RECRUITING

Philadelphia, Pennsylvania, 19107, United States
UC Irvine Health, Chao Family Comprehensive Cancer Center
RECRUITING

Orange, California, 92868, United States
UC San Diego Moores Cancer Center
RECRUITING

La Jolla, California, 92037, United States
UCLA Department of Medicine - Hematology/Oncology
RECRUITING

Los Angeles, California, 90095, United States
UCSF Helen Diller Family Comprehensive Cancer Center
RECRUITING

San Francisco, California, 94143, United States
UPMC
RECRUITING

Pittsburgh, Pennsylvania, 15232, United States
USC Norris Comprehensive Cancer Center
RECRUITING

Los Angeles, California, 90033, United States
Universitatsklinikum Mainz Hautklinik und Poliklinik
RECRUITING

Mainz, 55131, Germany
University Hospital Carl Gustav Carus Dresden
RECRUITING

Dresden, 01307, Germany
University of Colorado Hospital - Anschutz Cancer Pavilion
RECRUITING

Aurora, Colorado, 80045, United States
University of Iowa
RECRUITING

Iowa City, Iowa, 52242, United States
University of Kansas Cancer Center
RECRUITING

Westwood, Kansas, 66205, United States
University of Kiel
RECRUITING

Kiel, 24105, Germany
University of Louisville Brown Cancer Center
RECRUITING

Louisville, Kentucky, 40202, United States
University of Minnesota
RECRUITING

Minneapolis, Minnesota, 55455, United States
University of North Carolina at Chapel Hill
RECRUITING

Chapel Hill, North Carolina, 27514, United States
University of Tennessee
RECRUITING

Knoxville, Tennessee, 37920, United States
University of Texas Southwestern Medical Center
RECRUITING

Dallas, Texas, 75390, United States
University of Vermont Medical Center
RECRUITING

Burlington, Vermont, 05401, United States
Universitätsklinikum Essen
RECRUITING

Essen, 45147, Germany
Universitätsklinikum Hospital Heidelberg
RECRUITING

Heidelberg, 69120, Germany
Universitätsklinikum Medical Center
RECRUITING

Hamburg, 20246, Germany
Universitätsklinikum of Tübingen
RECRUITING

Tübingen, 72076, Germany
Uniwersyteckie Centrum Kliniczne
RECRUITING

Gdansk, 80-214, Poland
West Cancer Center and Research Institute
RECRUITING

Germantown, Tennessee, 38138, United States
West Virginia University
RECRUITING

Morgantown, West Virginia, 26506, United States
Winship Cancer Institute, Emory University
RECRUITING

Atlanta, Georgia, 30322, United States

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