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

e21543 Background: Acral melanoma, the most common subtype of cutaneous malignant melanoma in Asians, is often diagnosed at an advanced stage but responds poorly to current PD-1/PD-L1 inhibitors. Here, we report an open-label, multicenter, single-arm, phase Ib study, aiming to evaluate the safety and efficacy of the combination therapy of TQB2450, a humanized monoclonal antibody against PD-L1 and anlotinib, an anti-angiogenic oral multi-target tyrosine kinase inhibitor in patients with advanced acral melanoma. Methods: Eligible patients were adults (ECOG PS of 0 or 1) with pathologically confirmed metastatic acral melanoma. In this dose-escalation and cohort-expansion study, patients received TQB2450 1200mg every 3 weeks in combination with anlotinib 10mg or 12mg once daily, 2-week on/1-week off until conformed disease progression, unacceptable toxicity, or voluntary withdrawal. The primary end points were dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and objective response rate (ORR). The secondary end points included adverse events, disease control rate (DCR), progression-free survival (PFS), overall survival (OS). Results: By December 8, 2021, 19 patients has been enrolled. The majority of patients (16 of 19 patients) were naive to systemic therapy. No DLT was observed. Eighteen (95%) of 19 patients experienced treatment-related adverse events (TRAEs), but most were grade 1 or 2. The most common TRAEs were hypothyroidism, hypertension, blood triglyceride elevation, hyperglycemia, blood cholesterol elevation, neutropenia, blood uric acid elevation, bilirubin elevation. Grade 3 or greater TRAEs occurred in 6 patients (31.6%). Among all patients with advanced acral melanoma assessed by investigator according to RECIST version 1.1, two patients achieved confirmed complete response and two patients achieved confirmed partial response. The ORR were 21.1% (95% CI, 6.1% to 45.6%). The DCR was 73.7% (95% CI, 48.8% to 90.9%). The median PFS time was 5.5 months (95% CI, 2.8 months to not reached) per RECIST version 1.1. The median OS was 20.3 months (95% CI, 10.2 months to not reached). Conclusions: The combination of TQB2450 plus anlotinib showed promising benefit and was tolerable in patients with advanced acral melanoma, which needed further investigation of the combination therapy in advanced acral melanoma. Clinical trial information: NCT03991975.