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