Actively Recruiting
A Phase II Trial of Neoadjuvant Nivolumab and Ipilimumab Combined With Relatlimab for Patients With Resectable Advanced Melanoma Identified as Poor Responders to Immunotherapy
Led by Melanoma Institute Australia · Updated on 2026-02-19
494
Participants Needed
1
Research Sites
513 weeks
Total Duration
On this page
Sponsors
M
Melanoma Institute Australia
Lead Sponsor
B
Bristol-Myers Squibb
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating new combinations of immunotherapy for patients with resectable stage 3 cutaneous melanoma and any stage of mucosal melanoma. The study focuses on patients who can have surgery to remove all tumor deposits. The goal is to improve outcomes for patients who typically respond poorly to standard immunotherapy by testing neoadjuvant immunotherapy given before surgery to reduce recurrence. The trial tests six different immunotherapy combinations using the drugs nivolumab, relatlimab, ipilimumab, and pembrolizumab. These are given as two doses before surgery to stimulate the immune system to better attack melanoma cells. After surgery, patients may receive standard immunotherapy if the neoadjuvant treatment does not sufficiently reduce cancer cells. The study includes four phases: neoadjuvant treatment, surgery, possible adjuvant therapy, and long-term follow-up for up to 10 years. Participants will undergo assessments including biomarker testing, imaging, and pathology to evaluate tumor response at six weeks. Researchers will monitor survival, recurrence, side effects, and quality of life over 10 years. The study will also explore biomarkers in blood, tumor tissue, and stool to understand treatment response. A total of 493 patients will participate in this phase II trial conducted in Australia.
CONDITIONS
Brief Title
Neo IRENIE (NEOadjuvant Ipilimumab, RElatlimab, NIvolumab Evaluation)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Written informed consent
- Male or female patients at least 18 years old at consent
- Clinically detectable or imaging-confirmed melanoma
- Disease fully removable by surgery with tumor-free margins
- Up to 3 fully resectable in-transit metastases allowed
- Tumor accessible for new core biopsy for biomarker testing
- ECOG performance status 0 or 1
- Adequate blood, liver, kidney, and endocrine function
- Life expectancy greater than 12 months
- Women of childbearing potential must avoid pregnancy and breastfeeding during treatment
- Cohort 1: Stage IIIB, IIIC, IIID cutaneous melanoma with biomarker test predicting response
- Cohort 2: Stage IIIB, IIIC, IIID cutaneous melanoma with recurrence after anti-PD-1 therapy, no prior CTLA-4 or LAG-3 treatment
- Cohort 3: Any stage mucosal melanoma, fully resectable, no prior systemic treatment
You will not qualify if you...
- Diagnosis of uveal melanoma
- Contraindication to relatlimab, ipilimumab, or nivolumab
- Prior systemic therapy including anti-PD1/L1, anti-CTLA-4 or anti-LAG-3 (except anti-PD1 monotherapy in cohort 2)
- Immunodeficiency or recent systemic immunosuppressive therapy
- Active autoimmune disease requiring systemic treatment in past 12 months (with specific exceptions)
- Progressing additional cancers requiring recent treatment
- Known brain metastases or carcinomatous meningitis
- History or current pneumonitis or interstitial lung disease requiring steroids
- Active infection needing systemic therapy
- Known HIV, active Hepatitis B or C, or active tuberculosis
- Uncontrolled or significant cardiovascular disease
- Significant proteinuria unless low on quantitative testing
- Any condition or treatment interfering with study participation or results
- Psychiatric or substance abuse disorders interfering with cooperation
- Pregnant or breastfeeding females
- Medical or social conditions preventing scheduled assessments
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 4 to 5 weeks
Participants receive 2 doses of one of the new immunotherapy combinations before surgery to help the body recognize and destroy melanoma cells.
2 visits (in-person) for drug administration
Duration - 1 day
Participants undergo surgery to remove the melanoma and affected lymph nodes after completing neoadjuvant treatment.
1 surgical visit
Duration - Up to several months depending on response
Participants may receive standard immunotherapy after surgery if the neoadjuvant treatment did not clear enough cancer cells.
Visit schedule varies depending on treatment plan
Duration - Up to 10 years
Participants are followed for up to 10 years to monitor for melanoma recurrence and survival outcomes.
Periodic visits for monitoring over 10 years
Trial Site Locations
Total: 1 location
1
Melanoma Institute Australia
Wollstonecraft, New South Wales, Australia, 2065
Actively Recruiting
Research Team
M
Monica Osorio
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
6
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