Pembrolizumab in patients with advanced/metastatic acral lentiginous melanoma

Abstract

Background: The most common melanoma subtype in this locality is cutaneous acral lentiginous melanoma (ALM), which comprises of approximately 50-58% in reported series. In contrast, ALM accounts for only 2% to 3% of cases in Western populations. Prior studies established ALM as distinct from common cutaneous melanoma at the genomic level. Asian patients (pts) only accounted for 2% of the study population in the KEYNOTE-001 trial which investigated pembrolizumab (PEM) in ipilimumab-refractory patients (pts). Differing etiological and pathogenomic factors between subtypes of malignant melanomas may lead us to question the applicability of prior clinical trials data in ALM pts. No prior prospective trials of checkpoint inhibitors in ALM have been performed. We proposed a study to investigate the efficacy of PEM in ALM. Primary Objective: To determine the overall response rate (ORR) of pembrolizumab in biological treatment-naïve patients with ALM Secondary Objectives: (i) To assess the duration of response, (ii) the clinical benefit rate, (iii) progression-free survival, (iv) overall survival, (v) response as per Immune-related Response Criteria (irRC), and (vi) assessment of adverse events as per CTCAE vr. 4.0. Key Exploratory Objective: To determine baseline PD-L1 expressions in ALM. Trial design: Single-centre, open-labeled phase II study of PEM 200mg IV every 3 weeks (wks) in patients with advanced/metastatic ALM who have not had prior biological therapy. Mandatory tissue biopsy for correlative molecular analysis (KIT, BRAF, NRAS) and baseline PD-L1 expression is performed. On-treatment biopsy after 2 doses of PEM is also performed. Statistical & Sample Size Justifications: Simon’s Minimax two-stage design was used to calculate sample size. We consider PEM to be inactive if ORR is </= 10%, and active if ORR >/= 30%, assuming P0 = 0.10, P1= 0.30, and the type I error of 0.05 with power of 80%. 15 patients will be accrued in stage I, at which point a further 10 patients will be accrued if PEM is deemed not inactive. We aim to recruit a total of 28 patients. Study Progress: Approved by the NTEC-CUHK Ethics Committee. The first patient was recruited in February 2017.