A Phase 2 interventional study of Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination in Merkel Cell Carcinoma, sponsored by Melanoma Institute Australia. Recruiting at 1 site in Australia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-17.
Sponsored by Melanoma Institute Australia · Phase 2, Interventional, and Treatment
The goal of this clinical trial is to test neoadjuvant dual immunotherapy in Merkel cell carcinoma with the aim to improve recurrence-free survival
This is a phase 2, open label, single cohort, single centre, clinical trial of neoadjuvant immunotherapy with dual inhibition of PD-1 and LAG-3 immune checkpoint pathways. The hypothesis is that neoadjuvant therapy produces a higher pathological response rate (pCR) and a longer recurrence-free survival in a cohort of treatment-naïve patients with resectable stage I (≥10 mm) to stage III Merkel cell carcinoma compared to neoadjuvant nivolumab monotherapy in Checkmate 358 (n=123, NCT02488759, historical control).
135 studies on the registry are indexed under Carcinoma, Merkel Cell; 37 are open to participants now.
This study's planned enrollment of 20 is below the median of 40 across 118 interventional studies indexed under Carcinoma, Merkel Cell.
Browse Carcinoma, Merkel Cell studies →Melanoma Institute Australia is the lead sponsor of 16 studies on the registry; 7 are open to participants now.
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Nivolumab and relatlimab will be administered in a fixed dose combination (FDC). The FDC product contains nivolumab and relatlimab in a protein-mass ratio of 3:1 (nivolumab 240 mg and relatlimab 80 mg): in a 20 mL concentrate solution per single vial. The dose and dosing regimen for this study is nivolumab 480 mg and relatlimab 160 mg - 2 vials per infusion. This was primarily based on the observed benefit/risk profile observed in metastatic melanoma patients from Study CA224-020 pharmacokinetics (PK), pharmacodynamics, and extensive nivolumab monotherapy clinical experience. In addition, the Phase 2/3 Study CA224-047 established this dose as active in unresectable and metastatic melanoma. This study is open label and single arm, with all patients scheduled to receive two doses of nivolumab and relatlimab FDC prior to surgery on days 1 and 29.
Drug: Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination
Dual inhibition of the distinct LAG3 and PD-1 checkpoint pathways
Also known as: Opdualag
Pathological complete response rate
Proportion of patients with a pathological complete response, as determined on the week 6 surgical specimen using the guidelines published by the International Neoadjuvant Melanoma Consortium: Complete pathological response (pCR) = 0% viable tumour cells in the surgical specimen
Time frame: Week 6
Pathological non-complete response rate to neoadjuvant immunotherapy
Proportion of patients with each non-pCR response category, as determined on the week 6 surgical specimen using the guidelines published by the International Neoadjuvant Melanoma Consortium: * Near complete pathological response - (near pCR) - \>0% - ≤10% viable tumour * Partial pathological response (pPR) - \>10 - ≤50% viable tumour * Non pathological response (pNR) - \>50% viable tumour
Time frame: Week 6
Toxicity and tolerability of neoadjuvant immunotherapy
The treatment related adverse events (AE) as described in CTCAE version 5.0, from the initiation of study treatment up to 135 days after the last dose of study treatment
Time frame: Week 24
Objective response rate to neoadjuvant immunotherapy
The proportion of patients within each response category, as assessed using RECIST version 1.1, comparing week 6 to baseline CT and MRI. Objective response rate= CR and PR
Time frame: Week 6
Metabolic response rate to neoadjuvant immunotherapy
The proportion of patients within each response category, as assessed using PERCIST (standardised uptake value \[SUV\]) comparing week 6 to baseline PET. Metabolic response rate = CMR and PMR.
Time frame: Week 6
Recurrence-free survival
The proportion of patients alive and disease free from the time of surgery
Time frame: 10 years
Disease progression rate
1. The proportion of patients alive and with RECIST-defined progression of disease from the date of consent to the first radiographical evidence of local, regional or distant progression. 2. Disease progression which leads to unresectable MCC.
Time frame: Week 6
Event-free survival (EFS) rate
The proportion of patients with EFS defined as from the time of first dose of study treatment to the earliest of: 1. Disease progression to unresectable stage III or stage IV disease) 2. Recurrence of MCC 3. Treatment-related death 4. Disease related death
Time frame: 10 years
Overall survival rate
The proportion of patients alive at years 1, 2, 5 and 10, and to actual date of death (in months), from the initiation of study treatment.
Time frame: 10 years
Patient reported quality of life
1. Changes in patient rated quality of life scores using QLQ-C30 and EQ-5D-5L from date of consent to 6 -12 weekly intervals until the end of year 1. 2. The correlation of patient-rated quality of life scores with adverse events.
Time frame: 1 year
Study treatment completion rate
1. Proportion of patients receiving full neoadjuvant drug treatment per schedule and number of treatments missed. 2. Proportion of patients undergoing planned surgery at week 6. 3. Reasons for incomplete study treatment e.g. adverse event, withdrawn consent, , disease progression, patient lost to follow-up.
Time frame: Week 8
Surgical-related adverse events
Time frame: 12 weeks
Polyomavirus positivity
1. Proportion of patients with and without polyomavirus in tumour tissue at baseline. 2. Correlate Merkel cell polyomavirus viral positivity (MCPyV+) in stage I-III MCC with pathological response.
Time frame: Week 6
Biomarkers of response, resistance, toxicity
* Morphological assessment H\&E, including viable MCC cells, Ki67, TILs density, % fibrosis, % necrosis, compared with paired baseline measures. * Tumour PD-L1 expression status (+ve status = ≥1% tumour cells positive staining using Dako 28-8 PD-L1 IHC assay). * Characterisation of immune profile in tumour microenvironment using multiplex immunohistochemistry and Imaging mass cytometry. * RNA sequencing - gene expression profile including potential to perform single cell analysis on dissection specimen from tumour dissociates (single cell RNA seq). * Characterisation of peripheral immune profile through Cytometry by time of flight. * DNA sequencing to determine tumour mutational burden and key somatic mutations. * Response to treatment using circulating tumour DNA in peripheral blood using droplet digital PCR to quantify tumour DNA (copies/ml plasma) of known mutation in MCC tissue.
Time frame: Week 6
Correlation of gut microbiome on outcomes
1. Correlation of bacterial diversity and abundance with treatment response and incidence of treatment-related toxicities 2. Correlation of self-reported dietary habits (including use of oral probiotics) at baseline and impact on bacterial diversity in the gut 3. The use of antibiotics and/or steroids during neoadjuvant treatment and the impact on intestinal bacterial diversity and abundance
Time frame: Week 6
Correlation of outcome measures
Proportion of patients with concordance in pathological response, RECIST response and metabolic response (PERCIST)
Time frame: Week 6
Assessment of concordance between RECIST and immune-related response criteria
Proportion of patients with CR, PR, SD and PD as measured with both response criteria
Time frame: Week 6
Comparison of outcomes against CheckMate
Comparison of primary and secondary efficacy outcomes to those reported in the Checkmate 358 trial
Time frame: 10 years
Plan to share: No
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Melanoma Institute Australia