Neo IRENIE (NEOadjuvant Ipilimumab, RElatlimab, NIvolumab Evaluation)

NCT06999980 | Recruiting Phase 2 DMC

• 2 other identifiers: MIA2025/522CA224-1100
• Study Type: interventional
• Target: 494
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is for patients with stage 3 cutaneous melanoma and patients with mucosal melanoma who are able to have surgery to remove all tumour deposits. To improve the chance that melanoma will not recurr, new experimental combinations of a type of treatment called immunotherapy will be given before surgery.

Conditions

Mucosal Melanoma; Cutaneous Melanoma

Keywords

Neoadjuvant; Immunotherapy; Randomised trial; Low Responder

Outcome Measures

Primary Outcomes (1)

• Pathological response rate

  The primary endpoint is the pathological response rate at surgery (between days 43 and 56) from the first dose of neoadjuvant study treatment for each of cohorts 1b, 2 and 3. The pathological response is categorised thus: - Complete pathological response (pCR) - 0% viable tumour cells in the surgical specimen - Near complete pathological response - (near pCR) - \<10% viable tumour - Partial pathological response (pPR) - 10%-50% viable tumour - No pathological response (pNR) - \>50% viable tumour The proportion of participants with a pCR, or near pCR will determine the pathological response rate.

  Week 6

Secondary Outcomes (10)

• Event-free survival (EFS)

  10 years

• Objective response rate

  Week 6

• Metabolic response rate

  Week 6

• Loco-regional relapse-free survival

  10 years

• Distant metastases-free survival

  10 years

Study Arms (6)

Treatment Arm A

EXPERIMENTAL

Ipilimumab at 3 mg per kg with nivolumab at 1 mg per kg will be administered on days 1 and 22 (Q3W) in the neoadjuvant period for a total of 2 doses.

Drug: Ipilimumab 3mg/kg and nivolumab 1mg/kg

Treatment Arm B

EXPERIMENTAL

Ipilimumab 1mg per kg and the fixed dose combination nivolumab 480 mg and relatlimab 160 mg will be administered on days 1 and 29 (Q4W) for a total of 2 doses.

Drug: Ipilimumab 1mg/kg Nivolumab 480mg and relatlimab 160mg

Treatment Arm C

EXPERIMENTAL

Fixed dose combination of nivolumab 480 mg and relatlimab 160 mg alone, to be administered on days 1 and 29 (Q4W) for a total of 2 doses.

Drug: Nivolumab 480mg and relatlimab 160mg

Treatment Arm D (Cohort 1a)

ACTIVE COMPARATOR

Ipilimumab at 1 mg per kg with nivolumab at 3 mg per kg will be administered on days 1 and 22 (Q3W) in the neoadjuvant period for a total of 2 doses.

Drug: Ipilimumab 1mg/kg and nivolumab 3mg/kg

Treatment Arm E (Cohort 1b)

ACTIVE COMPARATOR

Ipilimumab at 1 mg per kg with nivolumab at 3 mg per kg will be administered on days 1 and 22 (Q3W) in the neoadjuvant period for a total of 2 doses.

Drug: Ipilimumab 1mg/kg and nivolumab 3mg/kg

Treatment Arm F

ACTIVE COMPARATOR

Pembrolizumab 200 mg will be administered on days 1 and 22 (Q3W) in the neoadjuvant period for a total of 2 doses

Drug: Pembrolizumab 200 mg

Interventions

Ipilimumab 3mg/kg and nivolumab 1mg/kg DRUG

Neoadjuvant for 2 doses on days 1 and 22

Also known as: Arm A

Treatment Arm A

Ipilimumab 1mg/kg Nivolumab 480mg and relatlimab 160mg DRUG

Neoadjuvant for 2 doses at days 1 and 29

Also known as: Arm B

Treatment Arm B

Nivolumab 480mg and relatlimab 160mg DRUG

Neoadjuvant for 2 doses on days 1 and 29

Also known as: Arm C

Treatment Arm C

Ipilimumab 1mg/kg and nivolumab 3mg/kg DRUG

Neoadjuvant for 2 doses at days 1 and 22

Also known as: Arm D (Cohort 1a)

Treatment Arm D (Cohort 1a); Treatment Arm E (Cohort 1b)

Pembrolizumab 200 mg DRUG

Neoadjuvant for 2 doses at days 1 and 22

Also known as: Arm F

Treatment Arm F

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Written informed consent
• \. Male or female patients who are at least 18 years of age on the day of signing informed consent.
• \. Clinically detectable disease, and/or RECIST version 1.1 defined disease, and/or disease confirmed on PET imaging.
• \. Fully resectable disease defined as having no significant vascular, central nervous system or bony involvement. Only cases where a complete surgical resection leading to tumour free margins and which is safely achieved is considered "resectable".
• \. Concurrent primary disease and lymph node metastases acceptable provided completely resectable.
• \. Up to 3 in-transit metastases are permitted as long as these are fully resectable.
• \. Tumour that is amenable to a newly obtained core biopsy for performance of the multi-omic predictive biomarker model
• \. ECOG performance status of 0 to 1.
• \. Adequate haematological, hepatic, renal and endocrine function
• \. An anticipated life expectancy of \>12 months.
• \. Women of child bearing potential (WOCBP) must agree to avoid pregnancy or breast feeding for the duration of study treatment.
• a. Histologically confirmed diagnosis of cutaneous melanoma or unknown primary melanoma
• b. AJCC 8th Ed Stage IIIB, IIIC, IIID cutaneous melanoma
• c. No prior systemic treatment for cutaneous melanoma
• d. Completion of the multi-omic predictive biomarker model within 14 days (7-10 business days) of planned randomisation.

You may not qualify if:

• \. Uveal melanoma
• \. Any contraindication to the administration of relatlimab, ipilimumab or nivolumab
• \. No prior systemic therapy, including treatment with prior anti-PD1/L1, anti-CTLA-4 or anti-LAG-3 therapy (cohorts 1 and 3), except for cohort 2 which will have received anti-PD1 monotherapy only.
• \. A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days of randomisation. The following are permitted:
• Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
• Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if patient is on a stable dose
• Non-absorbed intra-articular steroid injections.
• \. An active autoimmune disease that has required systemic treatment in the past 12 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). The following are permitted:
• Vitiligo
• Type I diabetes mellitus
• Residual autoimmune hypothyroidism on stable hormone replacement
• Resolved childhood asthma or atopy
• Psoriasis not requiring systemic treatment
• Autoimmune conditions which are not expected to recur in the absence of an external trigger.
• \. A known additional malignancy that is progressing or has required active treatment within the past 3 years. The following malignancies, if undergone successful definitive resection or curative treatment, are permitted:

Sponsors & Collaborators

• Melanoma Institute Australia: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Nivolumab; relatlimab; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Georgina Long

  Melanoma Institute Australia

  STUDY CHAIR

Central Study Contacts

Monica Osorio

CONTACT

+612 9911 7296; Monica.Osorio@melanoma.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 2, multicentre, 3 parallel cohorts, open label, randomised clinical trial of neoadjuvant therapy and using a multi-omic predictive biomarker test to identify patients with a 'high' or 'poor' likelihood of response to immunotherapy in one of the cohorts.

Study Record Dates

• First Submitted: May 23, 2025
• First Posted: May 31, 2025
• Study Start: February 9, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): January 1, 2038
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

AU (1)