Article Document Academic Article Information Content Entity Continuant Continuant Journal Article Entity Entity Generically Dependent Continuant 2025-05-08T13:55:47 RDF description of The combination of PAC-1 and entrectinib for the treatment of metastatic uveal melanoma - http://repository.healthpartners.com/individual/document-rn34269 10.1097/cmr.0000000000000927 Drugs and Drug Therapy <p>The treatment of metastatic uveal melanoma remains a major clinical challenge. Procaspase-3, a proapoptotic protein and precursor to the key apoptotic executioner caspase-3, is overexpressed in a wide range of malignancies, and the drug PAC-1 leverages this overexpression to selectively kill cancer cells. Herein, we investigate the efficacy of PAC-1 against uveal melanoma cell lines and report the synergistic combination of PAC-1 and entrectinib. This preclinical activity, tolerability data in mice, and the known clinical effectiveness of these drugs in human cancer patients led to a small Phase 1b study in patients with metastatic uveal melanoma. The combination of PAC-1 and entrectinib was tolerated with no treatment-related grade � 3 toxicities in these patients. The pharmacokinetics of entrectinib were not affected by PAC-1 treatment. In this small and heavily pretreated initial cohort, stable disease was observed in four out of six patients, with a median progression-free survival of 3.38 months (95% CI 1.6-6.5 months). This study is an initial demonstration that the combination of PAC-1 and entrectinib may warrant further clinical investigation. Clinical trial registration: Clinical Trials.gov: NCT04589832.<p> Melanoma Research 6 public Animal Studies 37474 The combination of PAC-1 and entrectinib for the treatment of metastatic uveal melanoma 21807 Cancer 33 Clinical Trials document-rn34269 Eye Diseases Skin Cancer 2023-10-31T22:14:21.843-05:00