Clinical Trial Finder

Inclusion Criteria:

• - Aged ≥ 18 years.

• - Written consent Histologically confirmed, resectable Merkel cell carcinoma with AJCC (8th ed) clinical stage I (≥ 10 mm), II, or III.

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

• - Measurable disease according to RECIST 1.1 criteria.

• - Tumour amenable to core biopsy.

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

• - 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.

Exclusion Criteria:

• - Clinical or radiographic 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.

• - 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

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).

Arms

Experimental: 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.

Interventions

Drug: - Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination

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