Kymera Therapeutics to present data from Phase 1 trial of KT-333

Kymera Therapeutics announced that new KT-333 Phase 1 data highlighting safety, pharmacokinetics, pharmacodynamics and clinical responses will be presented at the ASH 65th Annual Meeting and Exposition, taking place from December 9-12, 2023, in San Diego, California. Results released in an ASH abstract today include data as of a July 10, 2023 cut-off. The poster presentation is expected to include additional data, including PK/PD, safety and results of disease response assessments from additional patients subsequent to the abstract cut-off date. In addition, preclinical data will be presented supporting the potential of STAT3 protein degraders as a therapeutic approach in venetoclax-resistant Acute Myeloid Leukemia. Highlights of the KT-333 Clinical Abstract: The abstract reported Phase 1 data from 21 patients enrolled through dose level 5; 12 were evaluable for disease assessment, including 1 with cutaneous T-cell lymphoma and 1 with peripheral T-cell lymphoma (PTCL) at DL2, and 10 with solid tumors at DL1-4. Highlights include: One partial response reported after two cycles in a CTCL patient at DL2, and stable disease reported after two cycles in three solid tumor patients treated at DL3 and DL4. PD data in blood available for DL1-4 demonstrated robust, dose-dependent, and sustained STAT3 degradation in peripheral blood mononuclear cells that, particularly at DL3 and beyond, were at levels associated with anti-tumor activity in preclinical models. No dose limiting toxicities or serious adverse events were reported; the most common adverse events were Grade 1/2 constipation, fatigue, nausea, and anemia. These data provide evidence of STAT3 targeted protein degradation in humans with associated STAT3 pathway inhibition, along with early signs of antitumor activity, highlighting the potential of heterobifunctional degraders for targeting previously undruggable transcription factors.