Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma

Официальное название

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

Обзор

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

Подробное описание

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).

Вмешательства

• Препарат Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination
  Dual inhibition of the distinct LAG3 and PD-1 checkpoint pathways

Первичные конечные точки

• Pathological complete response rate [Срок оценки: Week 6]

Вторичные конечные точки (11)

• Pathological non-complete response rate to neoadjuvant immunotherapy [Срок оценки: Week 6]
• Toxicity and tolerability of neoadjuvant immunotherapy [Срок оценки: Week 24]
• Objective response rate to neoadjuvant immunotherapy [Срок оценки: Week 6]
• Metabolic response rate to neoadjuvant immunotherapy [Срок оценки: Week 6]
• Recurrence-free survival [Срок оценки: 10 years]
• Disease progression rate [Срок оценки: Week 6]
• Event-free survival (EFS) rate [Срок оценки: 10 years]
• Overall survival rate [Срок оценки: 10 years]
• Patient reported quality of life [Срок оценки: 1 year]
• Study treatment completion rate [Срок оценки: Week 8]
• Surgical-related adverse events [Срок оценки: 12 weeks]

Критерии участия

Критерии включения

• Aged ≥ 18 years
• Written consent
• Histologically confirmed, resectable Merkel cell carcinoma with AJCC (8th ed) clinical or pathological stage I (≥ 10 mm), IIA, or IIB or III disease
• In-transit metastases are permitted if they are completely resectable
• Measurable disease according to RECIST 1.1 criteria
• Previous radiotherapy permitted if there is RECIST-measurable progression of disease since the completion of radiotherapy
• 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.
• 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.

Критерии исключения

• Clinical, radiographic or pathological 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
• Troponin T (TnT) or I (TnI) >2 × institutional ULN
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis or current interstitial lung disease
• Has an active infection requiring systemic therapy
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• Melanoma Institute Australia — Wollstonecraft

Идентификаторы

NCT: NCT06151236 · MIA2023/489 · CA224-1064

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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