Purpose: Autophagy is a resistance mechanism to BRAF/MEK was 48.2% [95% confidence interval (CI), 31.0%–65.5%], median inhibition in BRAFV600-mutant melanoma. Here we used PFS was 11.2 months (95% CI, 5.4–16.9 months), and response rate hydroxychloroquine (HCQ) to inhibit autophagy in combination (RR) was 85% (95% CI, 64%–95%). The complete RR was 41% and with dabrafenib 150 mg twice daily and trametinib 2 mg every median overall survival (OS) was 26.5 months. In a patient with day (DþT). elevated LDH (n = 16), the RR was 88% and median PFS and OS Patients and Methods: We conducted a phase I/II clinical trial in were 7.3 and 22 months, respectively. four centers of HCQ þ DþT in patients with advanced BRAFV600-Conclusions: HCQ þ DþT was well tolerated and produced mutant melanoma. The primary objectives were the recommended a high RR but did not meet criteria for success for the one-year phase II dose (RP2D) and the one-year progression-free survival PFS rate. There was a high proportion of patients with pretreated (PFS) rate of >53%. and elevated LDH, an increasingly common demographic in Results: Thirty-four patients were evaluable for one-year PFS patients receiving targeted therapy. In this difficult-to-treat rate. Patient demographics were as follows: elevated lactate dehypopulation, the RR and PFS were encouraging. A randomized drogenase: 47%; stage IV M1c/M1d: 52%; prior immunotherapy: trial of DþT þ HCQ or placebo in patients with BRAFV600-50%. In phase I, there was no dose-limiting toxicity. HCQ 600 mg mutant melanoma with elevated LDH and previous immunoorally twice daily with DþT was the RP2D. The one-year PFS rate therapy is being conducted.