Approximately 30 subjects across approximately 5 United States (US) sites will be enrolled in the Phase 1 portion of the study and approximately 69-84 subjects across approximately 15 US sites will be enrolled in the Phase 2A portion of the study.~The Phase 1 portion of the study will follow a 3 + 3 dose-escalation design to evaluate twice-daily (BID) administration of LYC-55716 for DLTs and to determine the MTD and the RP2D for further assessment in Phase 2A. A treatment cycle will consist of 28 days of treatment and subjects may continue to receive subsequent cycles of therapy as long as they do not have clinically significant progressive disease.~In the Phase 2A portion of the study, 69-84 subjects with locally advanced or metastatic solid tumors considered most likely to be responsive to a RORγ agonist will be enrolled and treated at the MTD or RP2D.~Six cohorts of subjects with advanced cancer will be enrolled. Cohorts 1 to 3 will enroll 14 to 19 subjects per cohort. Tumor types include NSCLC (Cohort 1); gastric, esophageal and G-E junction adenocarcinoma (Cohort 2); and SCCHN (Cohort 3). Cohorts 4 to 6 will enroll up to 9 subjects per cohort. Tumor types include ovarian carcinoma (Cohort 4), renal cell carcinoma (Cohort 5), and urothelial carcinoma (Cohort 6).~Primary Study Objectives~Phase 1~Evaluate the safety and tolerability of LYC-55716~Determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)~Phase 2A~• Determine the objective response rate according to response evaluation criteria in solid tumors (RECIST) v1.1.~Secondary Study Objectives~Phase 1~Evaluate the activity of LYC-55716 by objective response according to RECIST v1.1.~Determine the durability of any observed objective response~Phase 2A~Determine the duration of response~Determine progression-free survival (PFS) and overall survival (OS)~Determine suitability of the RP2D for further study~Characterize the pharmacokinetics (PK) of LYC-55716
This is a Phase 1/2A study designed to evaluate the safety and tolerability of increased repeated doses of LYC-55716 in subjects with locally advanced or metastatic solid tumors.