Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma

NCT ID: NCT06151236

Last Updated: 2025-12-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-11
• Study Completion Date: 2034-04-30

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

Detailed Description

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).

Conditions

Merkel Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant Treatment

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.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

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

Interventions

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

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

Intervention Type: DRUG

Other Intervention Names

Opdualag

Eligibility Criteria

Inclusion Criteria

1. Aged ≥ 18 years

2. Written consent

3. Histologically confirmed, resectable Merkel cell carcinoma with AJCC (8th ed) clinical stage I (≥ 10 mm), IIA, or IIB or III disease

4. In-transit metastases are permitted if they are completely resectable

5. Measurable disease according to RECIST 1.1 criteria

6. Previous radiotherapy permitted if there is RECIST-measurable progression of disease since the completion of radiotherapy

7. ECOG 0-1

8. Adequate organ function on blood pathology

9. Life expectancy >12 months

10. Female patients to use effective contraception during study treatment and for 5 months after last dose.

Exclusion Criteria

1. Clinical or radiographic evidence of distant metastases

2. Contraindication to nivolumab and / or relatlimab

3. 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

4. Active autoimmune disease or requirement for chronic steroid therapy other than hormone replacement therapy

5. A diagnosis of immunodeficiency or chronic steroid therapy >10 mg OD prednisone or equivalent

6. Additional malignancy active within past 3 years; patients with chronic lymphocytic leukaemia can be included in this study.

7. Uncontrolled cardiovascular disease or history of myocarditis - Has had an allogenic tissue/solid organ transplant

8. Has had an allogenic tissue/solid organ transplant

9. Troponin T (TnT) or I (TnI) >2 × institutional ULN

10. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis or current interstitial lung disease

11. Has an active infection requiring systemic therapy

12. Active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.

13. Known HIV

14. Pregnant or breast feeding females

15. Concurrent medical or social conditions that may prevent the patient attending assessments or procedures per schedule

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Melanoma Institute Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Georgina V Long

Role: PRINCIPAL_INVESTIGATOR

Melanoma Instiute Australia

Locations

Melanoma Institute Australia

Wollstonecraft, New South Wales, Australia

Site Status: RECRUITING

Countries

Australia

Central Contacts

Monica Osorio

Role: CONTACT

monica.osorio@melanoma.org.au

+ 61 2 9911 7296

Facility Contacts

Monica Osorio

Role: primary

monica.osorio@melanoma.org.au

+612 9911 7296

Other Identifiers

CA224-1064

Identifier Type: OTHER

Identifier Source: secondary_id

MIA2023/489

Identifier Type: -

Identifier Source: org_study_id