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

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 toler-ated 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 attrib-uted to activation of the MAPK signalling pathway and transformation to an immu-nosuppressive tumour environment.Conclusions: TQB2450 combined with anlotinib showed favourable tolerance and promising anti-tumour activity with a prolonged PFS compared with anti- PD1 mon-otherapy in patients with advanced acral melanoma.