649TiP A phase I/Ib study evaluating the safety, pharmacokinetics, and preliminary efficacy of LP-118 in subjects with relapsed or refractory haematological malignancies

Newave Pharmaceutical is developing an investigational compound LP-118, a next generation selective B-cell lymphoma 2 (BCL-2) inhibitor with tuned extra-large (BCL-XL) activity to improve antitumor efficacy and reduce risk for thrombocytopenia. Clinical development of LP-118 includes targeting relapsed or refractory hematological malignancies. BCL-2 BCL-XL are important anti-apoptotic proteins in the intrinsic apoptotic pathway involved pathophysiology many hematologic malignancies, including Non-Hodgkin’s Lymphoma (NHL), Richter transformation (RT), multiple myeloma (MM), acute lymphoblastic leukemia (ALL), myeloid (AML), etc. (Valentin, Grabow et al. 2018). Considering that concern about acquired resistance venetoclax (the first FDA-approved indicated treatment AML has been obstacle patients, promising strategy overcoming mutation urgently needed (Tahir, Smith 2017) The inhibitory effect on targets carefully adjusted be between navitoclax aim minimizing on-target platelet toxicity while retaining improving efficacy. Pharmaceutical, Inc. intends conduct human study malignancies primary focus NHL, RT, MM, T-PLL, AML, ALL, MDS, MDS/MPN, MF. Phase Ia dose-escalation will begin Group 1 until DLT observed MTD established, RP2D OBD established. Once MTD, RP2D, established 1, phase dose escalation can proceed (hight risk). relapsed/refractory: low tumor lysis CLL/SLL; MF, CMML-2, MPN-BP, AML; T-PLL; ALL A classic “3+3” design used this study. safe starting calculated from non-clinical studies 50 mg/d. To mitigate TLS, accelerated step-up dosing schedule reach target each cohort. NCT04771572.