THESEUS PHARMACEUTICALS, INC. Theseus Pharmaceuticals, Inc. announced initial dose escalation data from the ongoing phase 1/2 trial of THE-630 in patients with advanced gastrointestinal stromal tumors (GIST). THE-630 is a pan-variant tyrosine kinase inhibitor (TKI) of the receptor tyrosine kinase KIT, designed for patients with GIST that have developed resistance to earlier lines of therapy. THE-630 Clinical Trial Background and Clinical Development Plan: Trial THE630-21-101 is a phase 1/2 open label, multicenter, first-in-human dose escalation and expansion trial designed to evaluate the safety, pharmacokinetics, and anti-tumor activity of oral THE-630 (NCT Number: NCT05160168).
The trial is expected to be conducted in two parts: a dose escalation phase, followed by an expansion phase. The patient population of the initial dose escalation phase (phase 1) of the trial will include patients with unresectable or metastatic GIST who had disease progression on or are intolerant to imatinib therapy and have also received at least one of the following: sunitinib, regorafenib, ripretinib, or avapritinib. The primary objective of the dose escalation phase is to determine the safety profile of THE-630, including the dose-limiting toxicities, maximum tolerated dose, and the recommended phase 2 dose.
Once a recommended dose has been determined in the dose escalation phase, the dose expansion phase (phase 2) will enroll patients with unresectable or metastatic GIST into three cohorts defined by prior therapy, including a second-line cohort and a fifth-line cohort. The primary objective of the expansion phase is to evaluate the anti-tumor activity of THE-630 in these GIST patient populations. Data from the phase 1/2 clinical trial is expected to inform further clinical development of THE-630 including the design of the planned registrational trials for THE-630.
Theseus is prioritizing the development of THE-630 in second-line GIST, where a pan-variant KIT inhibitor with activity against all major classes of activating, or cancer-causing, and resistance mutations has the potential to deliver meaningful clinical benefit over the current standard of care. Theseus also plans to evaluate THE-630 in fifth-line GIST, where there is currently no available therapy and therefore a significant unmet need.
