Theratechnologies Inc. has announced encouraging preliminary data from Part 3 of its Phase 1b trial of sudocetaxel zendusortide (TH1902) in patients with advanced ovarian cancer. The trial, designed to optimize weekly dosing, demonstrated favorable tolerability and early signs of efficacy in heavily pre-treated patients. The Medical Review Committee has unanimously recommended continued evaluation and exploration of higher doses based on these results.
Phase 1b Trial Design and Results
The Phase 1b trial enrolled 13 patients with advanced ovarian cancer who had progressed despite prior platinum-based and taxane chemotherapy. Patients were divided into two arms: Arm A received 1.75 mg/kg/week of sudocetaxel zendusortide, while Arm B received 2.5 mg/kg/week, both on a three-weeks-on/one-week-off schedule. No dose-limiting toxicities were observed in either arm.
While no responses were seen in the Arm A per-protocol (PP) set, three of six patients in the Arm B PP set showed encouraging activity. This included one patient with complete resolution of a liver lesion, significant reductions in the CA-125 ovarian tumor marker, and notable tumor shrinkage. Two patients in Arm B experienced more than a 25% reduction in tumor size. Patients in Arm B also received treatment for a longer duration, averaging 10.25 weeks compared to 7.6 weeks in Arm A.
Expert Commentary
"The latest data from Part 3 of the Phase 1 trial build on a compelling body of preclinical and translational evidence of antitumor activity with sudocetaxel zendusortide," said Ira Winer, M.D., Ph.D., FACOG, from Karmanos Cancer Center and Wayne State University School of Medicine. "While this is a small sample of patients, it is not often that we see promising signs of efficacy, combined with favorable safety and tolerability data, in this patient population with advanced disease. We therefore recommend and encourage continued investigation with further dose escalation for this agent."
Sudocetaxel Zendusortide and SORT1+ Technology
Sudocetaxel zendusortide is a first-in-class sortilin receptor (SORT1)-targeting peptide drug conjugate (PDC). It utilizes a cleavable linker to attach a proprietary peptide to docetaxel, a cytotoxic chemotherapeutic agent. The FDA has granted Fast Track designation to sudocetaxel zendusortide for treating all sortilin-positive recurrent advanced solid tumors refractory to standard therapy.
Theratechnologies' SORT1+ Technology™ platform is designed for developing PDCs that target SORT1, a receptor expressed in various tumor types, including endometrial, ovarian, colorectal, triple-negative breast, and pancreatic cancers. SORT1 expression is associated with aggressive disease and poor prognosis, making it an attractive target for anticancer drug development.
Future Plans
With significant clinical trial data now available, Theratechnologies plans to accelerate its search for a partner to advance its oncology program.
