Neo IRENIE (NEOadjuvant Ipilimumab, RElatlimab, NIvolumab Evaluation)

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMelanoma Institute Australia

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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".

Disqualifiers

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.

Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)

Trial design

Design model

Parallel

Treatments tested in this trial

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

    Drug

    Neoadjuvant for 2 doses on days 1 and 22

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

    Drug

    Neoadjuvant for 2 doses at days 1 and 29

  • Nivolumab 480mg and relatlimab 160mg

    Drug

    Neoadjuvant for 2 doses on days 1 and 29

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

    Drug

    Neoadjuvant for 2 doses at days 1 and 22

  • Pembrolizumab 200 mg

    Drug

    Neoadjuvant for 2 doses at days 1 and 22

Treatment groups

494 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Treatment Arm AExperimental treatment 1 intervention
Group B: Treatment Arm BExperimental treatment 1 intervention
Group C: Treatment Arm CExperimental treatment 1 intervention
Group D: Treatment Arm D (Cohort 1a)Active comparator 1 intervention
Group E: Treatment Arm E (Cohort 1b)Active comparator 1 intervention
Group F: Treatment Arm FActive comparator 1 intervention

Trial outcomes

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.

Time frame
Week 6

Secondary outcomes

1

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.

Time frame
10 years
2

Objective response rate

RECIST version 1.1 defined objective response at week 6 for patients with RECIST-measurable disease at baseline

Time frame
Week 6
3

Metabolic response rate

PERCIST defined metabolic response

Time frame
Week 6
4

Loco-regional relapse-free survival

Time from surgery to the date of loco-regional recurrence

Time frame
10 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Melanoma Institute Australia

Lead sponsor

Bristol-Myers Squibb

Collaborator