VO and Nivolumab vs Physician's Choice in Advanced Melanoma That Progressed on Anti-PD-1 & Anti-CTLA-4 Drugs (IGNYTE-3)

Advanced Melanoma Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06264180
• Other study ID #: RP1-104
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 1, 2024
• Est. completion date: August 31, 2034

Study information

• Verified date: January 2024
• Source: Replimune Inc.
• Contact: Clinical Trials at Replimune
• Phone: 1-781-222-9570
• Email: clinicaltrials[@]replimune.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: August 31, 2034
• Est. primary completion date: January 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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 (ß-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.

Related Conditions & MeSH terms

• Advanced Melanoma
• Melanoma

Intervention

Biological:
• 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.

Drug:
• Single-agent chemotherapy
Dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Replimune Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Time from the date of randomization to death due to any cause	Assessed up to January 2029, approximately 55 months
Secondary	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
Secondary	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