Clinical Research Directory

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 8 beginning in Cycle 2. Cycle 1 consists of pembrolizumab monotherapy to allow evaluation of early immunologic changes induced by PD-1 blockade without potential interference from irinotecan. Blood and tumor samples will be collected at baseline and prior to irinotecan administration on Cycle 2 Day 1 for translational immune analyses. Tumor assessments will be performed according to RECIST version 1.1 every 6 weeks during the first year and every 12 weeks thereafter. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), dose-limiting toxicity (DLT), and safety and tolerability as assessed by the incidence of adverse events graded according to CTCAE version 5.0. Exploratory analyses will evaluate tumor microenvironment characteristics and peripheral blood immune biomarkers, including immune cell phenotypes, cytokine profiles, and potential biomarkers associated with treatment response and resistance.

PICSTAT Pilot Study for CD8 PET/CT-Guided Lifileucel Treatment in Advanced Melanoma

This prospective, single-center pilot study is being performed to find out whether Zr-89 crefmirlimab berdoxam "CD8 PET/CT" scans can improve the effectiveness of the tumor-infiltrating lymphocyte (TIL) therapy called lifileucel ("Study Treatment") in treating metastatic melanoma. Participants must first provide consent to the companion protocol (UPCC 19426, PICSTAT CD8 PET) before being eligible to consent to this protocol.

Study Comparing Investigational Drug HBI-8000 + Nivolumab vs. Placebo + Nivolumab in Patients With Advanced Melanoma

This is a clinical study to compare the efficacy and safety of HBI-8000 combined with nivolumab to Placebo combined with nivolumab in patients with unresectable or metastatic melanoma. A separate open-label cohort of adults with new, progressive brain metastasis or adolescents with or without new progressive brain metastasis receive HBI-8000 combined with nivolumab.

A Study of ST-1898 for Unresectable or Metastatic Melanoma

ST-1898 is a receptor tyrosine kinase (RTK) inhibitor for multi-targets, especially for VEGFR2, c-MET, AXL, PDGFRA, RET, KIT etc. This trial is to evaluate its safety, tolerability, pharmacokinetic, and efficacy in subjects with unresectable or metastatic melanoma. In phase Ib, the primary objectives are to assess the safety and tolerability, and to determine Recommended Phase 2 dose (RP2D) of ST-1898 tablets in subjects with unresectable or metastatic melanoma. Secondary objectives are to assess the plasma concentration of ST-1898 and to evaluate the efficacy. In phase II, the primary objective is to assess the anti-tumor activities of ST-1898 tablets in subjects with unresectable or metastatic melanoma. The secondary objective is to evaluate the safety of ST-1898 tablets.