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]

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Melanoma
• Intervention / Treatment: Biological: Vusolimogene Oderparepvec; Biological: Nivolumab; Biological: Nivolumab + Relatlimab; Biological: Pembrolizumab; Drug: Single-agent chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials at Replimune; Phone Number: 1-781-222-9570; Email: clinicaltrials@replimune.com

Study Locations

• France
  • Bordeaux, France, 33075
    • Recruiting
    • CHU de Bordeaux, Hôpital Saint-André
    • Principal Investigator: Caroline Dutriaux, MD
  • Lille, France, 59000
    • Recruiting
    • CHU de Lille
    • Principal Investigator: Laurent Mortier, MD
  • Marseille, France, 13005
    • Recruiting
    • Hopital de la Timone
    • Principal Investigator: Caroline Gaudy, MD
  • Nice, France, 06200
    • Recruiting
    • CHU Nice
    • Principal Investigator: Henri Montaudie, MD
  • Paris, France, 75010
    • Recruiting
    • Hôpital Saint Louis - AP-HP
    • Principal Investigator: Celeste Lebbe, MD
  • Pierre-Bénite, France, 69495
    • Recruiting
    • Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
    • Principal Investigator: Stephane Dalle, MD
  • Villejuif, France, 94800
    • Recruiting
    • Institut Gustave Roussy
    • Principal Investigator: Caroline Robert, MD
• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charité - Universitätsmedizin Berlin
    • Principal Investigator: Thomas Eigentler, MD
  • Dresden, Germany, 01307
    • Recruiting
    • University Hospital Carl Gustav Carus Dresden
    • Principal Investigator: Friedegund Meier, MD
  • Erfurt, Germany, 99089
    • Recruiting
    • Helios Klinik
    • Principal Investigator: Rudolf Herbst, MD
  • Essen, Germany, 45147
    • Recruiting
    • Universitätsklinikum Essen
    • Principal Investigator: Dirk Schadendorf, MD
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitätsklinikum Medical Center
    • Principal Investigator: Christoffer Gebhardt, MD
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitätsklinikum Hospital Heidelberg
    • Principal Investigator: Jessica Hassel, MD
  • Kiel, Germany, 24105
    • Recruiting
    • University of Kiel
    • Principal Investigator: Katharina Kaehler, MD
  • Mainz, Germany, 55131
    • Recruiting
    • Universitatsklinikum Mainz Hautklinik und Poliklinik
    • Principal Investigator: Stephan Grabbe, MD
  • München, Germany, 80337
    • Recruiting
    • LMU München - Klinik and Poliklinik für Dermatologie und Allergologie, Dermatoonkologie
    • Principal Investigator: Lucie Heinzerling, MD
  • Tübingen, Germany, 72076
    • Recruiting
    • Universitätsklinikum of Tübingen
    • Principal Investigator: Andreas Meiwes, MD
• Greece
  • Athens, Greece, 11527
    • Recruiting
    • National and Kapodistrian University of Athens, General Hospital of Athens "Laiko"
    • Principal Investigator: Helen Gogas, MD
• Poland
  • Gdansk, Poland, 80-214
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne
    • Principal Investigator: Kamil Drucis, MD
  • Warsaw, Poland, 02-781
    • Recruiting
    • Maria Sklodowska-Curie National Research Institute of Oncology
    • Principal Investigator: Piotr Rutkowski, MD
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Principal Investigator: Eva Muñoz Couselo, MD
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic De Barcelona
    • Principal Investigator: Ana Arance, MD
  • El Palmar, Spain, 30120
    • Recruiting
    • Hospital Clínico Universitario Virgen de la Arrixaca
    • Principal Investigator: Pablo Cerezuela, MD
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Principal Investigator: Guillermo de Velasco, MD
  • Madrid, Spain, 28027
    • Recruiting
    • Clínica Universidad de Navarra - Madrid
    • Principal Investigator: Eduardo Castañón, MD
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Universidad de Navarra - Pamplona
    • Principal Investigator: Eduardo Castañón, MD
• United Kingdom
  • Liverpool, United Kingdom, L7 8YA
    • Recruiting
    • Clatterbridge Cancer Centre NHS Foundation Trust
    • Principal Investigator: Rafael Bach-Mora, MD
  • London, United Kingdom, SW3 6JJ
    • Recruiting
    • The Royal Marsden NHS Foundation Trust
    • Principal Investigator: James Larkin, MD
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • Royal Free London NHS Foundation Trust - Royal Free Hospital
    • Principal Investigator: Antonio Rullan, MD
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's & St. Thomas' NHS Foundation Trust
    • Principal Investigator: Benjamin Shum, MD
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
    • Principal Investigator: Patricio Serra, MD
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Recruiting
      • Banner MD Anderson Cancer Center
      • Principal Investigator: Fade Mahmoud, MD, FACP
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • UC San Diego Moores Cancer Center
      • Principal Investigator: Gregory Daniels, MD
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC Norris Comprehensive Cancer Center
      • Principal Investigator: Gino In, MD
    • Los Angeles, California, United States, 90025
      • Recruiting
      • The Angeles Clinic and Research Institute
      • Principal Investigator: Omid Hamid, MD
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Department of Medicine - Hematology/Oncology
      • Principal Investigator: Bartosz Chmielowski, MD
    • Orange, California, United States, 92868
      • Recruiting
      • UC Irvine Health, Chao Family Comprehensive Cancer Center
      • Principal Investigator: Thuy Tran, MD
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Cancer Institute
      • Principal Investigator: Allison Betof-Warner, MD
    • Sacramento, California, United States, 95816
      • Withdrawn
      • Sutter Medical Group
    • San Francisco, California, United States, 94143
      • Recruiting
      • UCSF Helen Diller Family Comprehensive Cancer Center
      • Principal Investigator: Katy Tsai, MD
    • San Francisco, California, United States, 94115
      • Recruiting
      • San Francisco Oncology Associates
      • Principal Investigator: Kevin Kim, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital - Anschutz Cancer Pavilion
      • Principal Investigator: Theresa Michelle Medina, MD
    • Englewood, Colorado, United States, 80113
      • Recruiting
      • The Melanoma and Skin Cancer Institute
      • Principal Investigator: Ryan Weight, DO
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • Medstar Washington Hospital Center
      • Principal Investigator: Suthee Rapisuwon, MD
  • Florida
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Memorial Cancer Institute at Memorial Regional Hospital
      • Principal Investigator: Atif Hussein, MD
    • Jacksonville, Florida, United States, 32207
      • Recruiting
      • Baptist MD Anderson Cancer Center
      • Principal Investigator: Konstantinos Chouliaras, MD
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Principal Investigator: Nikhil Khushalani, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute, Emory University
      • Principal Investigator: David Lawson, MD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern Memorial Hospital
      • Principal Investigator: Sunandana Chandra, MD
    • Park Ridge, Illinois, United States, 60068
      • Withdrawn
      • Advocate Lutheran General Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Principal Investigator: Mohammed Milhem, MBBS
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Recruiting
      • University of Kansas Cancer Center
      • Principal Investigator: Gary Doolittle, MD
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville Brown Cancer Center
      • Principal Investigator: Jason Chesney, MD, PhD
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Withdrawn
      • Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Corewell Health
      • Principal Investigator: Gerald Paul Wright, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Principal Investigator: Benjamin Manning, MD
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Recruiting
      • Dartmouth Hitchcock Cancer Center
      • Principal Investigator: Keisuke Shirai, MD
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Withdrawn
      • MD Anderson Cancer Center at Cooper
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center
      • Principal Investigator: Andrew L. Pecora, MD
    • Morristown, New Jersey, United States, 07960
      • Recruiting
      • Morristown Medical Center - Atlantic Health System
      • Principal Investigator: Eric Whitman, MD
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Principal Investigator: Michael Wong, MD
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Northwell Health, R.J. Zuckerberg Cancer Center
      • Principal Investigator: Shaheer Khan, MD
    • Stony Brook, New York, United States, 11794
      • Withdrawn
      • Stony Brook University Cancer Center
    • The Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center
      • Principal Investigator: Yvonne Saenger, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Principal Investigator: Frances Collichio, MD
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Cancer Center
      • Principal Investigator: Georgia Beasley, MD
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University- Martha Morehouse Tower
      • Principal Investigator: Merve Hasanov, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Principal Investigator: Anthony Olszanski, MD
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
      • Principal Investigator: Rino Seedor, MD
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • UPMC
      • Principal Investigator: Yana Najjar, MD
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
      • Principal Investigator: Maria Constantinou, MD
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Recruiting
      • West Cancer Center and Research Institute
      • Principal Investigator: David Portnoy, MD, FACP
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • University of Tennessee
      • Principal Investigator: Ardy Davarifar, MD, PhD
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Principal Investigator: Daniel Wang, MD
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology
      • Principal Investigator: Charles Cowey, MD
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Principal Investigator: Isabella Glitza, MD
  • Utah
    • Murray, Utah, United States, 84107
      • Recruiting
      • Intermountain Health
      • Principal Investigator: Caroline Nebhan, MD, PhD
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute
      • Principal Investigator: Elliot Asare, MD
    • St. George, Utah, United States, 84790
      • Withdrawn
      • St. George Regional Hospital
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Recruiting
      • University of Vermont Medical Center
      • Principal Investigator: Hibba tul Rehman, MD
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University
      • Principal Investigator: Joanna Kolodney, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VO + nivolumab	Biological: Vusolimogene Oderparepvec; Genetically modified Herpes Simplex Type 1 Virus.; Other Names: VO; RP1; Biological: Nivolumab; Anti-PD-1 Monoclonal Antibody; Other Names: Opdivo
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)	Biological: Nivolumab; Anti-PD-1 Monoclonal Antibody; Other Names: Opdivo; Biological: Nivolumab + Relatlimab; Nivolumab: Anti-PD-1 Monoclonal antibody. Relatlimab: A lymphocyte activation gene-3 (LAG-3) blocking antibody.; Other Names: Opdualag; Biological: Pembrolizumab; A programmed death receptor-1 (PD-1)-blocking antibody indicated.; Other Names: Keytruda; Drug: Single-agent chemotherapy; Dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from the date of randomization to death due to any cause	Assessed up to January 2029, approximately 55 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	The time from the date of randomization to the earliest date of the objective documentation of progressive disease (PD) per RECIST v1.1 or death due to any cause.	Assessed up to January 2029, approximately 55 months
Objective Response Rate (ORR)	The proportion of randomized patients with best overall response of complete response (CR) or partial response (PR) using the RECIST v1.1 criteria.	Assessed up to January 2029, approximately 55 months

Collaborators and Investigators

• Sponsor: Replimune, Inc.
• Investigators: Study Director: Jeannie Hou, MD, Replimune, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): August 31, 2034

Study Registration Dates

• First Submitted: January 29, 2024
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; pembrolizumab; relatlimab; Opdualag
• Other Study ID Numbers: RP1-104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No