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

Replimune

Status and phase: Enrolling; Phase 3

Conditions: Advanced Melanoma

Treatments: Biological: Vusolimogene Oderparepvec; Biological: Nivolumab; Biological: Pembrolizumab; Drug: Single-agent chemotherapy; Biological: Nivolumab + Relatlimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06264180

RP1-104

Details and patient eligibility

About

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.

Enrollment: 400 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 (β-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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

VO + nivolumab

Experimental group

Treatment:

Biological: Nivolumab

Biological: Vusolimogene Oderparepvec

Physicians Choice

Active Comparator group

Description:

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)

Treatment:

Biological: Nivolumab + Relatlimab

Drug: Single-agent chemotherapy

Biological: Pembrolizumab

Biological: Nivolumab