DT2216 BCL-XL degrader program
phase 1Develop a targeted anti-cancer therapy for relapsed or refractory malignancies, including patients with few or no other options, by selectively degrading BCL-XL while reducing platelet toxicity associated with BCL-XL inhibition.
Anti-apoptotic Protein Targeted Degradation compound that selectively degrades BCL-XL via the VHL E3 ligase; evaluated in an open-label Phase 1 dose-escalation and cohort-expansion clinical trial with IV twice-weekly dosing, RECIST v1.1 tumor assessments, pharmacokinetics, safety monitoring, and BCL-XL degradation measurement in peripheral leukocytes.
First-in-human Phase 1 study reported RP2D of 0.4 mg/kg IV twice weekly; site analysis also states DT2216 is in Phase 1/2 clinical trials for fibrolamellar carcinoma and platinum-resistant ovarian cancer.
In 20 enrolled patients, one dose-limiting grade 4 thrombocytopenia event resolved within 48 hours; stable disease was observed in 20% of patients; no bleeding episodes or treatment-emergent deaths were reported; DT2216 exposure was dose proportional with no accumulation; 0.4 mg/kg showed rapid and sustained BCL-XL degradation in peripheral leukocytes.