Cogent Biosciences, Inc. announced positive updated lead-in data from the company's ongoing Phase 3 PEAK trial evaluating the selective and potent KIT mutant inhibitor, bezuclastinib, in combination with sunitinib, in patients with Gastrointestinal Stromal Tumors (GIST). The data will be presented in a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL on June 1. Cogent also announced a new Phase 2 clinical trial of bezuclastinib plus sunitinib in later line GIST patients, sponsored by the Sarcoma Alliance for Research through Collaboration (SARC) and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute. PEAK is a randomized, open-label, global, Phase 3 clinical trial evaluating bezuclastinib in combination with sunitinib vs sunitinib alone in GIST patients previously treated with imatinib.

In the updated lead-in data being presented at ASCO, as of the cutoff date, April 1, 2024, the 42 patients in Part 1 have been on study for a median of 15.3 months. The median progression-free survival (mPFS) during treatment with bezuclastinib and sunitinib was 10.2 months in all patients. In a subset of second-line GIST patients with only prior imatinib, which most closely resembles patients currently enrolling in Part 2 of PEAK, the data demonstrate a mPFS of 19.4 months.

In addition, the objective response rate (ORR) in all patients treated with bezuclastinib and sunitinib was 27.5% and in the subset of second-line patients the ORR was 33.3%, per investigator assessment. Combination treatment resulted in a disease control rate of 80% in all patients and 100% in patients with prior imatinib only. As of the data cutoff, the combination of bezuclastinib and sunitinib does not appear to add to the severity of adverse events known to be associated with sunitinib monotherapy and is well-tolerated.

The majority of treatment-emergent adverse events (TEAEs) were low-grade and reversible. No additional serious adverse reactions or discontinuations due to TEAEs have been reported since the last presentation of data in November 2023. The open label, single arm Phase 2 trial sponsored by SARC and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute is designed to evaluate the mPFS as well as the safety and tolerability of bezuclastinib plus sunitinib in 40 patients with GIST who have previously progressed on sunitinib.

This trial will focus on later line patients, where limited treatment options are available. Enrollment continues in the Phase 3 registration-enabling PEAK study, which will include approximately 388 second-line, post imatinib GIST patients. Due to rapid enrollment, the Company now expects PEAK enrollment to be completed in the third quarter of 2024 with top-line results still expected by the end of 2025.

Cogent remains on-track to complete enrollment in APEX in patients with advanced systemic mastocytosis (AdvSM) by the end of 2024 and report top-line results mid-2025 and complete enrollment in SUMMIT Part 2 in the second quarter of 2025 and report top-line results by the end of 2025.