Clinical trial NCT06151236: Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma
Official title: A Phase 2, Open Label, Single Arm Clinical Trial of Neoadjuvant Nivolumab and Relatlimab in Stage I To III Resectable Merkel Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Merkel Cell Carcinoma
Lead sponsor: Melanoma Institute Australia
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2023-11-30
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label, single centre clinical trial
Primary purpose: TREATMENT

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

Detailed 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 criteria: 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

Primary outcomes:
measure: Pathological complete response rate
timeFrame: Week 6
Secondary outcomes:
measure: Pathological non-complete response rate to neoadjuvant immunotherapy
timeFrame: Week 6
measure: Toxicity and tolerability of neoadjuvant immunotherapy and surgery
timeFrame: Week 24
measure: Objective response rate to neoadjuvant immunotherapy
timeFrame: Week 6
measure: Metabolic response rate to neoadjuvant immunotherapy
timeFrame: Week 6
measure: Recurrence-free survival
timeFrame: 10 years
measure: Disease progression rate
timeFrame: Week 6
measure: Event-free survival rate
timeFrame: 10 years
measure: Overall survival rate
timeFrame: 10 years
measure: Patient reported quality of life
timeFrame: 1 year
measure: Study treatment completion rate
timeFrame: Week 8
Other outcomes:
measure: Polyomavirus positivity
timeFrame: Week 6
measure: Biomarkers of response, resistance, toxicity
timeFrame: Week 6
measure: Correlation of gut microbiome on outcomes
timeFrame: Week 6
measure: Correlation of outcome measures
timeFrame: Week 6
measure: Assessment of concordance between RECIST and immune-related response criteria
timeFrame: Week 6
measure: Comparison of outcomes against CheckMate
timeFrame: 10 years
Locations:
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
Study officials:
affiliation: Melanoma Instiute Australia
name: Ines Esteves Domingues Pires da Silva
role: PRINCIPAL_INVESTIGATOR
References: