Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma

A Phase 2, Open Label, Single Arm Clinical Trial of Neoadjuvant Nivolumab and Relatlimab in Stage I To III Resectable Merkel Cell Carcinoma

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).

Inclusion Criteria:

1. Aged ≥ 18 years
2. Written consent
3. Histologically confirmed, resectable Merkel cell carcinoma with AJCC (8th ed) clinical or pathological 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. 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.
8. ECOG 0-1
9. Adequate organ function on blood pathology
10. Life expectancy >12 months
11. Female patients to use effective contraception during study treatment and for 5 months after last dose.

Exclusion Criteria:

1. Clinical, radiographic or pathological 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
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