Kymera Therapeutics presents clinical data from Phase 1 trial of KT-333

Kymera Therapeutics shared new clinical data from its ongoing KT-333 Phase 1 trial. KT-333, a first-in-class, potent, highly selective, heterobifunctional small molecule degrader of STAT3, demonstrated antitumor responses in hematological malignancies with high unmet need, including relapsed/refractory classic Hodgkin’s lymphoma, cutaneous T-cell lymphoma, and NK-cell lymphoma, at doses that were well-tolerated. The data were presented at the European Hematology Association Annual Meeting, taking place from June 13-16, 2024, in Madrid, Spain. Results released in an EHA poster today include a data cut-off of June 3, 2024. The KT-333 Phase 1 clinical trial is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of KT-333 dosed weekly on 28-day cycles in adult patients with relapsed and/or refractory lymphomas, leukemias and solid tumors. The poster provides a clinical update as of June 3, 2024, from the ongoing KT-333 Phase 1 trial from 47 patients enrolled through seven dose levels with a mean of 9.1 doses. This includes patients with cHL, B-cell non-Hodgkin’s lymphoma, CTCL, peripheral T-cell lymphoma, large granular lymphocytic leukemia, T-cell prolymphocytic leukemia, NK-cell lymphoma, as well as solid tumors. Highlights from the poster include: Antitumor activity in patients with hematological malignancies evaluable for response: In cHL, complete responses were achieved in two of three patients at DL4. Both responders, who had received prior treatment with at least one regimen containing a check point inhibitor as well as brentuximab vedotin, have subsequently undergone stem cell transplantation. Additionally, stable disease was observed in a third cHL patient at DL6. In NK-cell lymphoma, one complete response was achieved at DL7 in a patient with STAT3 mutation. Among nine patients with CTCL, partial responses were achieved in four patients at DL2 and DL4-6, and stable disease was observed in one patient at DL4. In solid tumors, stable disease was observed in four of fourteen patients, including two head and neck tumor types as well as patients with cholangiocarcinoma and renal cell cancer, at DL3-4. Strong proof of mechanism with KT-333 achieving up to 95% mean maximum STAT3 degradation in peripheral blood mononuclear cells at DL7 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 as previously shown, suggestive of favorable immunomodulatory response in the tumor microenvironment following KT-333 treatment and supporting a potential novel combination partner with anti-PD-1 drugs in solid tumors. Dose dependent increases in KT-333 plasma exposure were observed, achieving levels predicted to be efficacious. KT-333 was well tolerated with primarily Grade 1 and 2 adverse events, including stomatitis and fatigue. Two dose-limiting toxicities, Grade 3 stomatitis and arthralgia, occurred in LGL-L patients at DL5 and one DLT, Grade 3 fatigue, was observed in a lymphoma patient treated at DL7. The Phase 1a trial for KT-333 is currently ongoing. The Company expects to complete the study and share additional clinical data to inform the program’s next development steps in 2024 at an upcoming medical meeting.