China-based Dizal Pharmaceutical Co., Ltd (SHA: 688192) presented updates on the clinical development of its JAK1 inhibitor golidocitinib (DZD4205) and DZD8586 at the 17th International Conference on Malignant Lymphoma (ICML) annual meeting.
Golidocitinib: A Promising Treatment for PTCL
Golidocitinib, the world’s first and only JAK1 inhibitor in regulatory trial stages, received fast-track status in the US in 2022. Peripheral T-cell lymphoma (PTCL), a type of malignant non-Hodgkin lymphoma (NHL), lacks effective treatment options. For patients with refractory/relapsed PTCL (r/rPTCL), the prognosis after initial treatment failure is extremely poor, with a five-year survival rate of less than 30%. In the efficacy evaluation involving 88 patients, the objective response rate (ORR) assessed by the Independent Review Committee (IRC) was 44.3% (39/88), with 21 cases achieving a complete response (CRR: 23.9%). The anti-tumor efficacy covered multiple common PTCL pathological subtypes. The median duration of remission (mDoR) has not been reached, with the longest remission duration recorded at 16.8 months. Safety analysis included 112 patients treated with golidocitinib, with a median relative dose intensity of 100% and the longest treatment duration of 18 months. Treatment-related adverse events (TRAEs) were predominantly hematology-related and mostly manageable.
DZD8586: A Selective Inhibitor Penetrating the Blood-Brain Barrier
DZD8586 is a highly selective small molecule inhibitor independently developed by Dizal Pharmaceutical, capable of completely penetrating the blood-brain barrier. It acts on both BTK-dependent and independent BCR signaling pathways, effectively inhibiting the growth of B-cell non-Hodgkin lymphoma (BBNHL) cells. Research results indicate that DZD8586 shows significant inhibitory effects on wild-type and mutated BTK, including those that lead to resistance against pirtobrutinib (LOXO-305). DZD8586 demonstrated encouraging initial anti-tumor effects and good safety in treated r/rB-NHL patients, expected to overcome BTK resistance issues. The pharmacokinetic characteristics were favorable and consistent with previous data from healthy subjects, and the safety profile was good, with no observed treatment-related adverse events of level 3 or above.-Fineline Info & Tech
