Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Combination Therapy With Pembrolizumab and Irinotecan in Patients With Metastatic or Recurrent Malignant Melanoma

This is a single-center, open-label, single-arm Phase 1b/2 clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of pembrolizumab in combination with irinotecan in patients with metastatic melanoma who have relapsed at least 6 months after completion of adjuvant pembrolizumab therapy or who are immune checkpoint inhibitor-naïve. The study consists of two sequential parts: a Phase 1b safety lead-in and a Phase 2 efficacy evaluation using Simon's optimal two-stage design. During the Phase 1b portion, six patients will be enrolled to assess the initial safety and tolerability of the combination regimen. Dose-limiting toxicities (DLTs) will be evaluated during the first two treatment cycles (42 days). Following completion of the safety observation period, a safety review will be conducted. If fewer than two of six patients experience a DLT, the regimen will be considered adequately tolerable and the study will proceed to the Phase 2 portion. Patients enrolled in the Phase 1b portion will be included in the efficacy analysis of Phase 2. In the Phase 2 portion, efficacy will be evaluated using Simon's optimal two-stage design with objective response rate (ORR) as the primary endpoint. The null hypothesis ORR is 30%, and the alternative hypothesis ORR is 50%, with a one-sided type I error rate of 5% and 80% power. In Stage 1, a total of 15 evaluable patients, including the six patients enrolled during the Phase 1b portion, will be assessed. If five or fewer objective responses are observed, the study will be terminated early for futility. If six or more responses are observed, additional patients will be enrolled in Stage 2. A total of 46 patients will be enrolled, and the regimen will be considered worthy of further investigation if at least 19 objective responses are observed. Participants will receive pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle. Irinotecan 125 mg/m² will be administered intravenously on Days 1 and