TH1902 in Patients With Advanced Solid Tumors

Summary

Participation Requirements

Description

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...

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, gynecological cancer (epithelial ovarian or endometrial cancer), colorectal cancer and pancreatic cancer that have relapsed or are refractory to standard chemotherapy, surgery, radiation therapy, and for which no known effective therapies exist. The PK profiles of TH1902 and free docetaxel will be evaluated for all patients in Parts 1 and 2. Once the MTD has been reached in Part 1, patients with TNBC, gynecological cancer (epithelial ovarian or endometrial cancer), colorectal cancer and pancreatic cancer (10 patients per cancer type) will be enrolled in Part 2 and treated at the MTD or RP2D to further assess the safety and tolerability of TH1902. The preliminary anti-tumor activity of TH1902 will be evaluated for all patients as per the response evaluation criteria in solid tumors (RECIST 1.1; Eisenhauer, 2009). The study will use a modified rapid dose-escalation design as described by Simon et al. (1997). 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 observed for 21 days post Cycle 1 Day 1 drug administration for dose limiting toxicity (DLT). Dose escalation to the next dose level will proceed following satisfactory review of safety data until the MTD is reached. The MTD is defined as that dose-level at which ?1 of 6 patients in a cohort develop an emergent DLT. Once the MTD has been defined, patients with TNBC, gynecological cancer (epithelial ovarian or endometrial cancer) colorectal cancer and pancreatic cancer may be treated at the MTD or Recommended Phase 2 Dose (RP2D), to further assess the safety and tolerability of TH1902, and the preliminary anti-tumor activity of TH1902.

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