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Theseus Pharmaceuticals Nixes Development of KIT Inhibitor THE-630

NEW YORK – Theseus Pharmaceuticals on Thursday said it was ending development of its pan-variant KIT inhibitor THE-630 in patients with gastrointestinal stromal tumors (GIST) and discontinuing enrollment in a Phase I/II study in which patients experienced dose-limiting toxicities.

The Phase I/II dose-escalation study of THE-630 involved patients with unresectable or metastatic GIST who had become resistant to prior KIT-targeted therapies.

Three patients receiving the 27 mg dose of THE-630 experienced grade 2 or grade 3 hand-foot skin reaction, which led to a dose interruption for one patient. Based on these toxicities, Theseus determined that the 27 mg dose exceeded the maximum-tolerated dose of THE-630. However, Theseus also said that THE-630 likely does not have a differentiated profile at doses below 27 mg because exposure to the drug at lower doses would be below the target level of 100 nanomolar average concentration.

Patients enrolled in the Phase I/II study will continue to receive THE-630 until a treatment discontinuation criterion is met, Theseus said. The firm is also analyzing data from the study to potentially inform the development of a low-dose formulation of THE-630 for KIT-associated mast cell-driven inflammatory indications.

"We are disappointed that we will not be able to achieve the target exposure for pan-variant inhibition with THE-630, as we continue to believe a therapy with potent activity against all major classes of activating and resistance mutations in KIT has the potential to confer significant clinical benefit, given the unmet need in GIST," Theseus CEO Tim Clackson said in a statement.

Theseus is developing another pan-variant KIT inhibitor candidate for GIST that is in the discovery stage. Clackson said the firm plans to nominate a development candidate in this program in the first half of 2024. The firm's other priorities include advancing the EGFR inhibitor THE-349 into clinical studies for non-small cell lung cancer and nominating a BCR-ABL-targeted candidate for leukemias.