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

Kymera Therapeutics announced that new Phase 1 data for KT-333, a first-in-class degrader of STAT3, highlighting safety, pharmacokinetics, pharmacodynamics and clinical responses will be presented at the European Hematology Association Annual Meeting, taking place from June 13-16, 2024, in Madrid, Spain. Results released in an EHA abstract today, which include a data cut-off as of February 6, 2024, demonstrate that KT-333 is a potent and selective STAT3 degrader that has demonstrated clinically significant responses in specific patient populations. 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. The abstract reported Phase 1 data from 39 patients enrolled through six dose levels with a mean of 8.7 doses, including patients with classic Hodgkin’s lymphoma, B-cell non-Hodgkin’s lymphoma, cutaneous T-cell lymphoma, peripheral T-cell lymphoma, large granular lymphocytic leukemia, T-cell prolymphocytic leukemia as well as solid tumors. Highlights include: Two complete responses in two cHL patients at DL4, three partial responses in CTCL patients at DL2, 4 and 5, and stable disease in four solid tumor patients at DL3-4. KT-333 achieved maximum degradation up to 97.5% in peripheral blood mononuclear cells at DL1-5 in Cycle 1 with evidence of STAT3 pathway inhibition and downregulation of inflammatory biomarkers in whole blood. Notably, KT-333 resulted in robust reduction of STAT3, pSTAT3, and SOCS3 expression in a CTCL tumor biopsy in DL4. Induction of an IFN-gamma stimulated gene signature predictive of sensitivity to anti-PD1 was seen in both peripheral blood and tumor, suggestive of favorable immunomodulatory response in the tumor microenvironment following KT-333 treatment. Dose dependent increases in KT-333 plasma exposure were observed, achieving levels predicted to be efficacious. KT-333 was generally well-tolerated with the most common adverse events being stomatitis, nausea, ALT increase, constipation and fatigue. Two dose-limiting toxicities were observed at DL5 including Grade 3 stomatitis and arthralgia in two separate LGL-L patients. No DLTs were observed in lymphoma or solid tumor patients at the time of the cut-off. Grade 3 stomatitis was also the only KT-333 related serious adverse event.