Neoadjuvant immunotherapy for 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

This study is testing a combination of two immune treatments to see if they can help people with a type of skin cancer called Merkel cell carcinoma have better outcomes before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Melanoma Institute Australia (Academic / other)
• Drugs / interventions: nivolumab, relatlimab, chemotherapy, prednisone, immunotherapy
• Locations: 1 site (Wollstonecraft, New South Wales)
• Trial ID: NCT06151236 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial investigates the effectiveness of neoadjuvant dual immunotherapy using nivolumab and relatlimab in patients with resectable Merkel cell carcinoma. The study aims to improve recurrence-free survival by targeting PD-1 and LAG-3 immune checkpoint pathways. Participants will receive a fixed dose combination of nivolumab and relatlimab prior to surgical resection, with the hypothesis that this approach will yield a higher pathological response rate compared to previous monotherapy treatments. The trial is conducted at a single center and includes treatment-naïve patients with specific staging criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed, resectable stage I to III Merkel cell carcinoma.

Not a fit: Patients with distant metastases or prior exposure to certain immunotherapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve recurrence-free survival rates for patients with Merkel cell carcinoma.

How similar studies have performed: Previous studies have shown promise with immunotherapy approaches in similar conditions, but this specific dual therapy is novel.

Eligibility criteria

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

Where this trial is running

Wollstonecraft, New South Wales

• Melanoma Institute Australia — Wollstonecraft, New South Wales, Australia (Recruiting)

Study contacts

• Principal investigator: Georgina V Long — Melanoma Instiute Australia
• Study coordinator: Monica Osorio

Conditions Merkel Cell Carcinoma