On June 9, 2023 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported that new and updated clinical data related to two novel investigational hematological malignancy therapies, HMPL-306 and amdizalisib, will be presented at the upcoming European Hematology Association (EHA) (Free EHA Whitepaper) ("EHA") Annual Meeting, taking place June 8-11, 2023 in Frankfurt, and the 17th International Conference on Malignant Lymphoma ("ICML") taking place June 13-17, 2023 in Lugano (Press release, Hutchison China MediTech, JUN 9, 2023, View Source [SID1234632612]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

HMPL-306: first in human results

Title:

A phase 1 study of HMPL-306, a dual inhibitor of mutant isocitrate dehydrogenase (IDH) 1 and 2, in pts with relapsed/refractory myeloid hematological malignancies harboring IDH1 and/or 2 mutations

Lead Author:

Lijuan Hu, MD, Peking University People’s Hospital Graphic

Meeting:

EHA poster presentation

Session:

Myeloproliferative neoplasms – Clinical

Abstract # & Link:

Abstract #P539

Mutations in isocitrate dehydrogenase ("IDH") 1/2 are frequently identified in various cancers, such as acute myeloid leukemia ("AML"), cholangiocarcinoma, chondrosarcoma and glioma. Mutant IDHs cause accumulated 2-hydroxyglutarate, leading to blockage of cell differentiation, thereby inducing malignant transformation. Mutant IDH isoform switching, from mutant IDH1 to mutant IDH2 and vice versa, have been reported as a mechanism of acquired resistance to IDH inhibition in AML and cholangiocarcinoma, as well as cases initially carrying co-existing mutations.

Preclinical data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (AACR 2023) demonstrated that HMPL-306 is a potent, durable, dual inhibitor of IDH1/2 mutation that crosses the blood brain barrier and affects pharmacodynamic ("PD") markers that lead to the differentiation of immature malignant cells to mature normal cells. It is being evaluated in clinical trials (NCT04272957, NCT04762602, NCT04764474).

This first-in-human, dose-escalation study data presents HMPL-306 in patients with relapsed/refractory myeloid hematological malignancies harboring IDH1 and/or IDH2 mutations. Based on PD, pharmaco­kinetic ("PK"), and preliminary clinical findings, a recommended Phase II dose was nominated for the dose expansion phase of the study.

Amdizalisib: updates from Phase Ib

Title:

Updated results from a phase 1b study of amdizalisib, a novel inhibitor of phospho­inositide 3-kinase-delta (PI3Kδ), in patients with relapsed or refractory lymphoma

Lead Author:

Junning Cao, MD, Fudan University Shanghai Cancer Center

Meeting:

ICML Publication

Session:

Phase I-II trials

Abstract #:

Abstract #653

Amdizalisib (HMPL-689) is a novel, selective and potent oral inhibitor targeting the isoform PI3Kδ. Amdizalisib’s PK properties are favorable with good oral absorption, moderate tissue distribution and low clearance in preclinical PK studies, suggesting a low risk of drug accumulation and drug-to-drug interaction. Because of its high target selectivity and optimal PK profile, amdizalisib has the potential to demonstrate an optimal benefit-risk profile in this class. Amdizalisib is currently being evaluated in a Phase II registration trial in relapsed or refractory follicular lymphoma ("FL") and marginal zone lymphoma ("MZL") as a single agent (NCT04849351), as well as in combination with tazemetostat (a methyl­trans­ferase inhibitor of EZH2) in patients with relapsed or refractory lymphoma in a Phase II study in China (NCT05713110).

Here we report updated results from a Phase Ib study of amdizalisib in patients with various subtypes of non-Hodgkin’s lymphoma ("NHL"). In this update, more mature data were available from the FL cohorts, at median follow-up duration of 22.1 months. Median duration of response ("DoR") and progression free survival ("PFS") were not reached for the 26 efficacy evaluable patients in the FL cohort. PFS and DoR from the MZL cohort were presented for the first time, at median follow-up duration of 20.3 months. Median DoR was not reached and median PFS was 26.8 months for the 16 efficacy evaluable patients in the MZL cohort. Safety data were reported from 153 patients with median exposure duration of 8.7 months. The most common treatment emergent adverse events (TEAEs) of Grade ≥3 (≥5%) were pneumonia (15.7%), neutrophil count decreased (12.4%), lipase increased (7.8%), and rash (5.9%). The treatment discontinuation rate due to adverse events was 11.8%.