Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma

Melanoma Institute Australia

Status and phase: Enrolling; Phase 2

Conditions: Merkel Cell Carcinoma

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06151236

MIA2023/489

CA224-1064 (Other Identifier)

Details and patient eligibility

About

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

Full 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).

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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. 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 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
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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Neoadjuvant Treatment

Experimental group

Description:

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.

Treatment:

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