This first-in-human study is designed as a multi-center, open-label, with 2 sequential parts:~Part 1 (dose escalation): will comprise patients with recurrent advanced solid tumors (all comers) that have relapsed or are refractory to standard chemotherapy, surgery, radiation therapy, and for which no known effective therapies exist.~Part 2 (expansion): will comprise selected patient populations with recurrent advanced TNBC, HR+ breast cancer, epithelial ovarian cancer, endometrial cancer, cutaneous melanoma, thyroid cancer, SCLC, prostate cancer and other cancers known to express SORT1 that are refractory to standard therapy.~The PK profiles of TH1902 and free docetaxel will be evaluated for all patients in Parts 1 and 2. PK samples will be obtained from patients before and after the dose of TH1902 administered at Cycles 1 and 3 and at odd Cycles beyond Cycle 3 in Part 1, and at odd Cycles in Part 2. Part 1 of this study will use a modified rapid dose-escalation design. A starting dose of 30 mg/m2 is proposed based on the available data for TH1902 and the known safety profile of docetaxel. Dose escalation by dose-doubling will be done for the first 2 dose levels, followed by a modified Fibonacci dose escalation scheme (i.e. dose increases of 67%, 50%, 40% and 33%) thereafter for each dose level. Patients in Part 1 will be monitored for 21 days post Day 1 drug administration of each cycle for study drug toxicity. Dose escalation to the next dose level will proceed following satisfactory review of safety data by the Medical Review Committee (MRC) until the maximum tolerated dose (MTD) is reached. If ≥2 patients in a dose escalation cohort experience an emergent dose-limiting toxicity (DLT) by Day 21 of the first treatment cycle, dose escalation will stop, and the prior dose level will be declared as the MTD. Intermediate dose levels may also be explored. The MTD is defined as the highest dose level at which ≤1 of 6 patients in a dose-level cohort develop an emergent DLT. The dose selection for Part 2 of this study will be based on the MTD and other available data. Once the MTD has been determined in Part 1, patients in Part 2 will be treated at the immediate dose level below the MTD, to further assess the safety and tolerability of TH1902 and the preliminary anti-tumor activity of TH1902. The anti-tumor activity will be evaluated for all patients as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Open label first-in-human study of TH1902 in solid cancer, with 2 sequential parts:~Part 1 (dose escalation): patients with recurrent advanced solid tumors (all comers) that have relapsed or are refractory to standard chemotherapy, surgery, radiation therapy, and for which no known effective therapies exist.~Part 2 (expansion): selected patient populations with recurrent advanced TNBC, HR+ breast cancer, epithelial ovarian cancer, endometrial cancer, cutaneous melanoma, thyroid cancer, SCLC, prostate cancer and other cancers known to express SORT1 that are refractory to standard therapy