Cutaneous MelanomaPhase 2Neo IRENIENCT06999980
Neo IRENIE (NEOadjuvant Ipilimumab, RElatlimab, NIvolumab Evaluation)
A Phase 2 study testing Ipilimumab 3mg/kg and nivolumab 1mg/kg, Ipilimumab 1mg/kg Nivolumab 480mg and relatlimab 160mg and Nivolumab 480mg and relatlimab 160mg in people with Cutaneous Melanoma and Mucosal Melanoma, run by Melanoma Institute Australia at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous Melanoma, Mucosal Melanoma
- What is being tested?
- Ipilimumab 3mg/kg and nivolumab 1mg/kg, Ipilimumab 1mg/kg Nivolumab 480mg and relatlimab 160mg and Nivolumab 480mg and relatlimab 160mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 494 participants
- Where
- 1 siteAustralia
- Study dates
- 9 Feb 2026to Jan 2038
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Written informed consent
- 2. Male or female patients who are at least 18 years of age on the day of signing informed consent.
- 3. Clinically detectable disease, and/or RECIST version 1.1 defined disease, and/or disease confirmed on PET imaging.
- 4. 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".
- 5. Concurrent primary disease and lymph node metastases acceptable provided completely resectable.
- 6. Up to 3 in-transit metastases are permitted as long as these are fully resectable.
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- 7. Tumour that is amenable to a newly obtained core biopsy for performance of the multi-omic predictive biomarker model
- 8. ECOG performance status of 0 to 1.
- 9. Adequate haematological, hepatic, renal and endocrine function
- 10. An anticipated life expectancy of >12 months.
- 11. 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.
- a. Histologically confirmed diagnosis of cutaneous melanoma or unknown primary melanoma
- b. AJCC 8th Ed Stage IIIB, IIIC, IIID cutaneous melanoma
- c. Disease progression on neoadjuvant anti-PD-1 monotherapy, where progressed disease is completely resectable or, disease recurrence on adjuvant anti-PD-1 monotherapy, where recurrent disease is completely resectable
- d. No prior treatment with CTLA-4 or LAG-3 inhibitors.
- a. Histologically confirmed diagnosis of mucosal melanoma
- b. Any stage of disease provided it is fully resectable
- c. No prior systemic treatment for mucosal melanoma
- COMMON Exclusion Criteria Applicable to all 3 cohorts
- 1. Uveal melanoma
- 2. Any contraindication to the administration of relatlimab, ipilimumab or nivolumab
- 3. 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.
- 4. 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.
- 5. 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.
- 6. 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:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy)
- Prostatic intraepithelial neoplasia
- In situ melanoma
- Atypical melanocytic hyperplasia
- Multiple primary melanomas
- Other malignancies for which the patient has been disease free for 1 year.
- 7. A known CNS metastases and/or carcinomatous meningitis
- 8. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis or current interstitial lung disease.
- 9. Has an active infection requiring systemic therapy.
- 10. Has a known history of Human Immunodeficiency Virus (HIV). Note: no testing for HIV is required unless mandated by local health authority.
- 11. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- 12. Has a known history of active TB (Bacillus Tuberculosis).
- 13. Uncontrolled or significant cardiovascular disease including, but not limited to any of the following:
- Myocardial infarction (MI) or stroke/transient ischemic attack within the 6 months prior to consent
- Uncontrolled angina within the 3 months prior to consent
- Any history of clinically significant arrhythmias (such as poorly controlled atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
- QTc prolongation > 480 ms
- History of other clinically significant cardiovascular disease (i.e. cardiomyopathy, congestive heart failure with New York Heart Association functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled venous thrombosis, etc)
- Cardiovascular disease-related requirement for daily supplemental oxygen
- History of 2 or more M.I.s OR 2 or more coronary revascularisation procedures (regardless of the number of stent placements during each procedure)
- Patients with history of myocarditis, regardless of aetiology.
- 14. Patients with a >1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is <1 g/24 hours.
- 15. Has a 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.
- 16. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 17. Pregnant or breast feeding females
- 18. Concurrent medical or social conditions that may prevent the patient from attending assessments per schedule
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site, 1 recruiting
- Recruiting
Melanoma Institute Australia
Wollstonecraft, New South Wales, 2065
Monica Osorio Clinical Trials Operations Manager, +612 2 9911 7296, Monica.Osorio@melanoma.org.au
About this study
Official title: A Phase II, Multicentre, Parallel Group, Open Label, Randomised Clinical Trial of Neoadjuvant Nivolumab and Ipilimumab Combined With Relatlimab for Patients With Resectable Advanced Melanoma Identified as Poor Responders to Immunotherapy
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.
Read the detailed description
This clinical trial is for patients with cutaneous melanoma which has spread to the lymph nodes (known as stage 3 melanoma) and for patients with any stage of mucosal melanoma. The study is for those patients who have disease that can be surgically removed.
The standard treatment for these patients is surgery to remove the affected tumour, lymph nodes, and any other deposits of melanoma, followed by drug therapy (known as adjuvant therapy). The most common drug therapy used to treat melanoma after surgery is known as 'immunotherapy'. Immunotherapy works by boosting the body's own immune system to better recognise and kill cancer cells.
The aim of the study is to offer new immunotherapy combinations to 3 cohorts of patients who are known to be poor responders to standard immunotherapy regimens.
Three cohorts of patients will be included:
- Patients with resectable stage 3 cutaneous melanoma who have a predictive biomarker test result that indicates: Cohort 1a - they will be poor responders to standard anti-PD-1 immunotherapy (n=168) Cohort 1b - they will be high responders to standard anti-PD-1 immunotherapy (n=~154)
- Patients with resectable stage 3 cutaneous melanoma who have had a recurrence of melanoma despite having standard anti-PD-1 based immunotherapy (n=111).
- Patients with resectable mucosal melanoma, at any stage of disease. Mucosal melanoma is known to respond poorly to stabdard immunotherapy (n=60).
This research will test 6 combinations of immunotherapy which are given before surgery. Treatment given before surgery is known as 'neoadjuvant' treatment. Neoadjuvant treatment is standard for many cancers, including melanoma. The purpose of neoadjuvant immunotherapy is to increase the body's natural immune response by training it to recognise the evasive cancer cells before they are removed at surgery, and to shrink or destroy the melanoma, which may make surgery easier. This has been shown to reduce the chance of melanoma recurring after surgery. The drugs used in this study are called 'nivolumab', 'relatlimab', and 'ipilimumab' and 'pembrolizumab'
In this trial, there are 5 different study treatment combinations. Each combination uses different mechanisms to potentially overcome the predicted resistance to standard immunotherapy. There are 4 phases to the study:
- Neoadjuvant treatment with one of the new immunotherapy combinations
- Surgery
- Adjuvant treatment with standard immunotherapy, IF the neoadjuvant therapy has not been effective enough to clear more than 10% of cancer cells.
- Follow up for recurrence and survival to the end of 10 years
The main goal is to learn which of the new immunotherapy combinations are most effective at destroying the melanoma cells before surgery for each cohort of patients.
The other important goals are to learn which treatment is best at preventing the return of melanoma over 10 years and which increases survival from melanoma. The investigators also want to evaluate the side effects patients may have to treatment and how this affects the quality of life. The investigators will also continue to research biomarkers in blood, tumour tissue and stools to identify possible mechanisms for better response to therapy.
The study will be conducted in Australia and a total of 493 patients will be involved.
- Conditions
- Cutaneous Melanoma, Mucosal Melanoma
- Being tested
- Ipilimumab 3mg/kg and nivolumab 1mg/kg, Ipilimumab 1mg/kg Nivolumab 480mg and relatlimab 160mg, Nivolumab 480mg and relatlimab 160mg, Ipilimumab 1mg/kg and nivolumab 3mg/kg, Pembrolizumab 200 mg
- Keywords
- Neoadjuvant, Immunotherapy, Randomised trial, Low Responder
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ipilimumab 3mg/kg and nivolumab 1mg/kgDrug
Also called Arm A
Neoadjuvant for 2 doses on days 1 and 22
Ipilimumab 1mg/kg Nivolumab 480mg and relatlimab 160mgDrug
Also called Arm B
Neoadjuvant for 2 doses at days 1 and 29
Nivolumab 480mg and relatlimab 160mgDrug
Also called Arm C
Neoadjuvant for 2 doses on days 1 and 29
Ipilimumab 1mg/kg and nivolumab 3mg/kgDrug
Also called Arm D (Cohort 1a)
Neoadjuvant for 2 doses at days 1 and 22
Pembrolizumab 200 mgDrug
Also called Arm F
Neoadjuvant for 2 doses at days 1 and 22
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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 Receives: Drug: Pembrolizumab 200 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 6
Secondary outcomes (10)
Event-free survival (EFS)
The proportion of patients with the earliest EFS outcome of: (a) Melanoma progression from randomisation and prior to planned surgery (b) Disease recurrence, from the date of surgery (local, regional or distant). (c) Study treatment-related death from randomisation. (d) Melanoma-related death, from randomisation.
Measured: 10 years
Objective response rate
RECIST version 1.1 defined objective response at week 6 for patients with RECIST-measurable disease at baseline
Measured: Week 6
Metabolic response rate
PERCIST defined metabolic response
Measured: Week 6
Loco-regional relapse-free survival
Time from surgery to the date of loco-regional recurrence
Measured: 10 years
Distant metastases-free survival
Time from surgery to the earliest date of distant recurrence, treatment-related death, or melanoma-related death
Measured: 10 years
Overall survival
Time from randomisation to death
Measured: at 1, 2, 5 and 10 years
Type, frequency and severity of drug-related toxicities
The number, type, and grade of treatment-related adverse events per CTCAE version 5.0
Measured: 30 days from last dose of study treatment
Surgical adverse outcomes
The number and grade of surgical complications according to the Clavien-Dindo Classification assessed at 3, 12 and 48 weeks post-operatively
Measured: At 3, 12 and 48 weeks post-operatively
Health related quality of life
The individual, summary and composite scores obtained from the validated EUROQOL QLQ-C30, EQ-5D, FACT-M (questions M10 to M17)
Measured: 1 year
Comparison of the actual pathologocal response to each immunotherapy arm with the predicted pathological response to neoadjuvant immunotherapy based on the multi-omic predictive biomarker model
Correlation of the actual pathological response with the predicted response to combination neoadjuvant immunotherapy based on the multi-omic predictive biomarker model
Measured: Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2025
- Study start9 Feb 2026
- Primary completionMar 2028 (estimated)
- Study completionJan 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 494 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Melanoma Institute Australia
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Georgina Long, Study chair, Melanoma Institute Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06999980
- Sponsor's protocol ID
- MIA2025/522
- Other IDs
- CA224-1100
- Acronym
- Neo IRENIE
- Status last verified
- Feb 2026
- First submitted
- 23 May 2025
- Last updated
- 19 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multicentre, Parallel Group, Open Label, Randomised Clinical Trial of Neoadjuvant Nivolumab and Ipilimumab Combined With Relatlimab for Patients With Resectable Advanced Melanoma Identified as Poor Responders to Immunotherapy
- ClinicalTrials.gov ID
- NCT06999980
- Acronym / sponsor ID
- Neo IRENIE / MIA2025/522
- Conditions
- Cutaneous Melanoma, Mucosal Melanoma
- Keywords
- Neoadjuvant, Immunotherapy, Randomised trial, Low Responder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 494 participants (estimated)
- Lead sponsor
- Melanoma Institute AustraliaUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 9 Feb 2026 (actual)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Jan 2038 (estimated)
- First posted
- 31 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This clinical trial is for patients with cutaneous melanoma which has spread to the lymph nodes (known as stage 3 melanoma) and for patients with any stage of mucosal melanoma. The study is for those patients who have disease that can be surgically removed.
The standard treatment for these patients is surgery to remove the affected tumour, lymph nodes, and any other deposits of melanoma, followed by drug therapy (known as adjuvant therapy). The most common drug therapy used to treat melanoma after surgery is known as 'immunotherapy'. Immunotherapy works by boosting the body's own immune system to better recognise and kill cancer cells.
The aim of the study is to offer new immunotherapy combinations to 3 cohorts of patients who are known to be poor responders to standard immunotherapy regimens.
Three cohorts of patients will be included:
- Patients with resectable stage 3 cutaneous melanoma who have a predictive biomarker test result that indicates: Cohort 1a - they will be poor responders to standard anti-PD-1 immunotherapy (n=168) Cohort 1b - they will be high responders to standard anti-PD-1 immunotherapy (n=~154)
- Patients with resectable stage 3 cutaneous melanoma who have had a recurrence of melanoma despite having standard anti-PD-1 based immunotherapy (n=111).
- Patients with resectable mucosal melanoma, at any stage of disease. Mucosal melanoma is known to respond poorly to stabdard immunotherapy (n=60).
This research will test 6 combinations of immunotherapy which are given before surgery. Treatment given before surgery is known as 'neoadjuvant' treatment. Neoadjuvant treatment is standard for many cancers, including melanoma. The purpose of neoadjuvant immunotherapy is to increase the body's natural immune response by training it to recognise the evasive cancer cells before they are removed at surgery, and to shrink or destroy the melanoma, which may make surgery easier. This has been shown to reduce the chance of melanoma recurring after surgery. The drugs used in this study are called 'nivolumab', 'relatlimab', and 'ipilimumab' and 'pembrolizumab'
In this trial, there are 5 different study treatment combinations. Each combination uses different mechanisms to potentially overcome the predicted resistance to standard immunotherapy. There are 4 phases to the study:
- Neoadjuvant treatment with one of the new immunotherapy combinations
- Surgery
- Adjuvant treatment with standard immunotherapy, IF the neoadjuvant therapy has not been effective enough to clear more than 10% of cancer cells.
- Follow up for recurrence and survival to the end of 10 years
The main goal is to learn which of the new immunotherapy combinations are most effective at destroying the melanoma cells before surgery for each cohort of patients.
The other important goals are to learn which treatment is best at preventing the return of melanoma over 10 years and which increases survival from melanoma. The investigators also want to evaluate the side effects patients may have to treatment and how this affects the quality of life. The investigators will also continue to research biomarkers in blood, tumour tissue and stools to identify possible mechanisms for better response to therapy.
The study will be conducted in Australia and a total of 493 patients will be involved.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm A | Experimental | Drug: Ipilimumab 3mg/kg and nivolumab 1mg/kgIpilimumab 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. |
| Treatment Arm B | Experimental | Drug: Ipilimumab 1mg/kg Nivolumab 480mg and relatlimab 160mgIpilimumab 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. |
| Treatment Arm C | Experimental | Drug: Nivolumab 480mg and relatlimab 160mgFixed 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. |
| Treatment Arm D (Cohort 1a) | Active comparator | Drug: Ipilimumab 1mg/kg and nivolumab 3mg/kgIpilimumab 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. |
| Treatment Arm E (Cohort 1b) | Active comparator | Drug: Ipilimumab 1mg/kg and nivolumab 3mg/kgIpilimumab 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. |
| Treatment Arm F | Active comparator | Drug: Pembrolizumab 200 mgPembrolizumab 200 mg will be administered on days 1 and 22 (Q3W) in the neoadjuvant period for a total of 2 doses |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (66 listed)
- 1. Written informed consent
- 2. Male or female patients who are at least 18 years of age on the day of signing informed consent.
- 3. Clinically detectable disease, and/or RECIST version 1.1 defined disease, and/or disease confirmed on PET imaging.
- 4. 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".
- 5. Concurrent primary disease and lymph node metastases acceptable provided completely resectable.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ipilimumab 3mg/kg and nivolumab 1mg/kgAlso: Arm ANeoadjuvant for 2 doses on days 1 and 22 | Drug | Treatment Arm A |
| Ipilimumab 1mg/kg Nivolumab 480mg and relatlimab 160mgAlso: Arm BNeoadjuvant for 2 doses at days 1 and 29 | Drug | Treatment Arm B |
| Nivolumab 480mg and relatlimab 160mgAlso: Arm CNeoadjuvant for 2 doses on days 1 and 29 | Drug | Treatment Arm C |
| Ipilimumab 1mg/kg and nivolumab 3mg/kgAlso: Arm D (Cohort 1a)Neoadjuvant for 2 doses at days 1 and 22 | Drug | Treatment Arm D (Cohort 1a), Treatment Arm E (Cohort 1b) |
| Pembrolizumab 200 mgAlso: Arm FNeoadjuvant for 2 doses at days 1 and 22 | Drug | Treatment Arm F |
Primary outcome
Pathological response rate
Time frame: Week 6
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.
10 secondary outcomes
Event-free survival (EFS)
Time frame: 10 years
Objective response rate
Time frame: Week 6
Metabolic response rate
Time frame: Week 6
Loco-regional relapse-free survival
Time frame: 10 years
Distant metastases-free survival
Time frame: 10 years
Overall survival
Time frame: at 1, 2, 5 and 10 years
Type, frequency and severity of drug-related toxicities
Time frame: 30 days from last dose of study treatment
Surgical adverse outcomes
Time frame: At 3, 12 and 48 weeks post-operatively
Health related quality of life
Time frame: 1 year
Comparison of the actual pathologocal response to each immunotherapy arm with the predicted pathological response to neoadjuvant immunotherapy based on the multi-omic predictive biomarker model
Time frame: Week 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Georgina Long study chair
Melanoma Institute Australia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ipilimumab 3mg/kg and nivolumab 1mg/kg, Ipilimumab 1mg/kg Nivolumab 480mg and relatlimab 160mg and Nivolumab 480mg and relatlimab 160mg in people with Cutaneous Melanoma and Mucosal Melanoma, run by Melanoma Institute Australia at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 66 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Monica Osorio (+612 9911 7296, Monica.Osorio@melanoma.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological response rate (time frame: Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.