Kymera Therapeutics to present new clinical data for KT-253 at ASCO

Kymera Therapeutics announced new clinical data for KT-253, a first-in-class MDM2 degrader, from its ongoing Phase 1 dose escalation trial will be presented at the American Society of Clinical Oncology Annual Meeting, taking place from May 31 – June 4, 2024, in Chicago, Illinois. Results released in an ASCO abstract today include a data cut-off of January 26, 2024. The abstract reported Phase 1 data from 18 patients including 13 patients in Arm A (solid tumors and lymphomas) at dose levels (DL) 1-4, and 5 patients in Arm B (high grade myeloid malignancies) at DL1-2 as of January 26, 2024. The most common solid tumor types were Merkel cell carcinoma (MCC) in 3 patients, adenoid cystic carcinoma (ACC) in 2 patients, and uveal melanoma in 2 patients. Highlights include: Disease Response Assessments: Arm A: One partial response confirmed in a MCC patient in DL1. Additionally, 3 stable diseases were reported for patients with fibromyxoid sarcoma, ACC, and renal cell cancer in DL1-3, respectively. Arm B: One confirmed complete response in DL2 and one confirmed partial response in DL1, both in patients with post-myeloproliferative neoplasm (MPN) acute myeloid leukemia (AML). Pharmacodynamic (PD) data from Arm A (DL1-4) and Arm B (DL1-2) demonstrated rapid upregulation of plasma GDF-15 protein and upregulation of CDKN1A and PHLDA3 mRNA levels in blood. KT-253 demonstrated dose-dependent increase in plasma exposure with levels approximating projected efficacious doses. KT-253 was generally well-tolerated with the most common adverse events (AEs) including nausea, fatigue, headache, and vomiting. There was 1 dose-limiting toxicity (DLT) of AEs leading to discontinuation that included Grade 2 nausea and fatigue in Arm A DL4. There were no neutropenia or thrombocytopenia AEs in either Arm. KT-253 related serious adverse events (SAEs) included Grade 3 hypotension in a patient with decreased oral intake in Arm A DL1.