A phase 2 study of neoadjuvant nivolumab + relatlimab versus nivolumab in patients with resectable high-risk basal cell carcinoma.

Abstract

TPS9613 Background: The high response rate of neoadjuvant anti-PD-1 has changed the management of locally advanced cutaneous squamous cell carcinoma. However, little is known about the benefit of neoadjuvant immunotherapy for basal cell carcinoma (BCC). Anti-PD-1 is approved second line for advanced BCC where it has modest response rates compared to the first line setting. High LAG-3 expression within the BCC tumor microenvironment may function as a subdominant checkpoint to synergize with anti-PD-1. The current randomized prospective multicenter phase 2 trial evaluates the safety and efficacy of neoadjuvant nivolumab (anti-PD-1) + relatlimab (anti-LAG-3) versus nivolumab alone in resectable high-risk BCC. Methods: This multicenter study conducted across the University of California Melanoma and Skin Cancer Consortium will enroll up to 30 patients with resectable high-risk BCC. High-risk BCC is defined by size 2.0 cm or greater in the head and neck region or 4.0 cm or greater for the trunk and extremities. All patients must have surgically resectable disease that is at increased risk for cosmetic disfigurement, functional defects, poor oncologic control, or anticipated to require skin grafting or free flap reconstruction. Patients must also be checkpoint and hedgehog inhibitor naïve with ECOG performance status of <2. Key exclusion criteria include recent radiation therapy and any prior history of myocarditis. Patients will be randomized in 2:1 fashion to receive nivolumab 480 mg + relatlimab 160 mg or nivolumab 480 mg IV every 4 weeks for up to 4 doses. Patients may forgo surgery and continue beyond 4 doses for up to 1 year in cases of ongoing clinical benefit. Tumor tissue and peripheral blood will be interrogated for immune cell subsets and checkpoint expression before and after neoadjuvant treatment. The trial’s primary endpoint is the combined rate of pathological complete response, major pathologic response, and clinical response following neoadjuvant therapy with secondary endpoints including surgical de-escalation, safety, duration of response, and recurrence-free survival. This trial uses a Simon’s minimax two-stage design for the nivolumab + relatlimab cohort. Eleven patients will be enrolled in the first stage. If ≥2 patients respond to nivolumab + relatlimab, the study will continue enrollment for a total of 20 patients. This design yields a type I error rate of 0.1 and power of 0.8. This study was approved by UC San Diego’s Institutional Review Board; approval number is 810617. Trial Registration NCT06624475. Clinical trial information: NCT06624475 .