Phase Ib study of anlotinib in combination with anti‐PD‐L1 antibody (TQB2450) in patients with advanced acral melanoma

Abstract Background Acral melanoma, the most common subtype of melanoma in Asians, is often diagnosed at an advanced stage and responds poorly to current programmed cell death protein 1 (PD‐1) inhibitors. Objectives To evaluate the safety and efficacy of TQB2450 and anlotinib in patients with advanced acral melanoma in a phase Ib study (NCT03991975). Methods Patients received TQB2450 (1200 mg every 3 weeks) and anlotinib (10 mg or 12 mg once daily, 2‐week on/1‐week off) in the dose‐escalation and dose‐expansion phases. The primary endpoints were dose‐limiting toxicity (DLT), maximum tolerated dose (MTD) and objective response rate (ORR). Results Nineteen patients were enrolled between June 2019 and June 2022. The majority of patients (16 of 19 patients) received anlotinib and TQB2450 as first‐line treatment. No DLTs were observed, and MTD was not reached. Eighteen (94.7%) out of 19 patients experienced treatment‐related adverse events (TRAEs), but most were grade 1 or 2. Grade 3 or greater TRAEs occurred in seven patients (36.8%). The ORR was 26.3% (two complete responses and three partial responses). The disease control rate was 73.7%. The median duration of response was 30.3 months [95% confidence interval (CI): 5.8–NA]. The median progression‐free survival (PFS) was 5.5 months (95% CI: 2.8–NA), and median overall survival was 20.3 months (95% CI: 14.8–NA). Whole‐exome sequencing suggested that acquired drug resistance might be attributed to activation of the MAPK signalling pathway and transformation to an immunosuppressive tumour environment. Conclusions TQB2450 combined with anlotinib showed favourable tolerance and promising anti‐tumour activity with a prolonged PFS compared with anti‐PD1 monotherapy in patients with advanced acral melanoma.