Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma

NCT06151236 | Recruiting Phase 2 DMC

• 2 other identifiers: MIA2023/489CA224-1064
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test neoadjuvant dual immunotherapy in Merkel cell carcinoma with the aim to improve recurrence-free survival

Conditions

Merkel Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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

  Week 6

Secondary Outcomes (11)

• Pathological non-complete response rate to neoadjuvant immunotherapy

  Week 6

• Toxicity and tolerability of neoadjuvant immunotherapy

  Week 24

• Objective response rate to neoadjuvant immunotherapy

  Week 6

• Metabolic response rate to neoadjuvant immunotherapy

  Week 6

• Recurrence-free survival

  10 years

Other Outcomes (6)

• Polyomavirus positivity

  Week 6

• Biomarkers of response, resistance, toxicity

  Week 6

• Correlation of gut microbiome on outcomes

  Week 6

Study Arms (1)

Neoadjuvant Treatment

EXPERIMENTAL

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

Interventions

Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination DRUG

Dual inhibition of the distinct LAG3 and PD-1 checkpoint pathways

Also known as: Opdualag

Neoadjuvant Treatment

Eligibility Criteria

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

You may qualify if:

• Aged ≥ 18 years
• Written consent
• Histologically confirmed, resectable Merkel cell carcinoma with AJCC (8th ed) clinical or pathological stage I (≥ 10 mm), IIA, or IIB or III disease
• In-transit metastases are permitted if they are completely resectable
• Measurable disease according to RECIST 1.1 criteria
• Previous radiotherapy permitted if there is RECIST-measurable progression of disease since the completion of radiotherapy
• At least one of either, archival tissue from a primary or nodal MCC lesion (if applicable) for the current diagnosis and/or a newly obtained core biopsy of a lesion which has not been previously irradiated.
• ECOG 0-1
• Adequate organ function on blood pathology
• Life expectancy \>12 months
• Female patients to use effective contraception during study treatment and for 5 months after last dose.

You may not qualify if:

• Clinical, radiographic or pathological evidence of distant metastases
• Contraindication to nivolumab and / or relatlimab
• Prior anti-PD-1, CTLA-4, PDL-1 or LAG 3 antibody exposure, or an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease or any chemotherapy or experimental local or systemic drug treatment
• Active autoimmune disease or requirement for chronic steroid therapy other than hormone replacement therapy
• A diagnosis of immunodeficiency or chronic steroid therapy \>10 mg OD prednisone or equivalent
• Additional malignancy active within past 3 years; patients with chronic lymphocytic leukaemia can be included in this study.
• Uncontrolled cardiovascular disease or history of myocarditis
• Has had an allogenic tissue/solid organ transplant
• Troponin T (TnT) or I (TnI) \>2 × institutional ULN
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis or current interstitial lung disease
• Has an active infection requiring systemic therapy
• Active Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
• Known HIV
• Pregnant or breast feeding females
• Concurrent medical or social conditions that may prevent the patient attending assessments or procedures per schedule

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

Carcinoma, Merkel Cell

Interventions

Nivolumab; relatlimab; Opdualag

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

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 V Long

  Melanoma Instiute Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica Osorio

CONTACT

+ 61 2 9911 7296; monica.osorio@melanoma.org.au

Study Design

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

Model Details: Open label, single centre clinical trial

Study Record Dates

• First Submitted: November 21, 2023
• First Posted: November 30, 2023
• Study Start: March 11, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 1, 2034
• Last Updated: February 17, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)