Apatinib combined with camrelizumab in advanced acral melanoma patients: An open-label, single-arm phase 2 trial
Mené sur 30 patients atteints d'un mélanome acral lentigineux malin de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement de première ligne combinant apatinib et camrélizumab
Background : At present, immune monotherapy and combination therapy did not show satisfactory effects on acral melanoma, and still no standard treatment is available for advanced acral melanoma. Here, a phase II trial was performed to explore the safety and efficacy of apatinib combined with camrelizumab in advanced acral melanoma patients as first-line therapy(NCT03955354). Methods: Patients with pathologically confirmed locally unresectable or metastatic treatment native acral melanoma received 250 mg apatinib once daily and camrelizumab 200 mg once every two weeks intravenously every 28-day cycle. The primary endpoint was objective response rate (ORR), the secondary endpoints were disease control rate (DCR), overall survival (OS), progression-free survival (PFS) and safety. Results: Thirty patients were recruited between January 2015 and January 2022. Among them, 21 (70.0%) had stage IV, and the median tumor burden was 50 mm (range: 11-187). The ORR was 24.1%, and 7 of 29 patients had an anti-tumor response, including partial response (n=5) and complete response (n=2). The DCR was 82.8%, median PFS was 7.5 months (CI: 2.7-12.3), and median OS was 13.4 months (CI: 1.9-25.0). Grade 3-4 treatment-related toxicity(grade 3 50.5%;grade 4 3.3%) included transaminase elevations, proteinuria, leukocytopenia, vomiting, diarrhea and drug-induced liver injury. No treatment-related mortality occurred. The mutations of TTN, MUC16, VPS13D, ALPK2 and SCUBE1 showed significant alterations with survival outcome. Conclusions : Apatinib combined with camrelizumab showed manageable safety profile and reasonable anti-tumor activity in advanced acral melanoma patients as first-line therapy.