On April 29, 2021 Hutchison China MediTech Limited ("HUTCHMED") (Nasdaq/AIM: HCM) reported that it has initiated a registration-intent Phase II clinical trial of HMPL-689, its highly selective and potent PI3Kδ inhibitor, in China in patients with relapsed or refractory follicular lymphoma ("FL") and marginal zone lymphoma ("MZL"), two subtypes non-Hodgkin’s lymphoma ("NHL") (Press release, Hutchison China MediTech, APR 29, 2021, View Source [SID1234583630]). The first patient was dosed today .
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The clinical trial is a multi-center, single-arm, open-label clinical study to evaluate the efficacy and safety of HMPL-689 once a day oral monotherapy in approximately 100 patients with relapsed/refractory FL and approximately 80 patients with relapsed/refractory MZL. Relapsed/refractory is defined when a patient has not achieved response (complete response or partial response) after the latest line of systemic treatment, or has progressive disease or relapse after achieving response. The primary endpoint is objective response rate ("ORR"), with secondary endpoints including complete response rate (CRR), progression-free survival (PFS), time to response (TTR) and duration of response (DoR). The trial is being conducted in over 35 sites in China. More information will be available at clinicaltrials.gov, using identifier NCT04849351.
The initiation of the Phase II trial is based on the highly promising preliminary results from the Phase Ib expansion study ongoing in China, which show that HMPL-689 was well tolerated, exhibiting dose-proportional pharmacokinetics ("PK"), a manageable toxicity profile, and single-agent clinical activity in relapsed/refractory B-cell lymphoma patients. Additional details may be found at clinicaltrials.gov, using identifier NCT03128164.
About PI3Kδ and NHL
PI3Kδ (phosphoinositide 3-kinase delta) is a lipid kinase that controls the activation of several important signaling proteins. Upon an antigen binding to B-cell receptors, PI3Kδ can be activated through the Lyn and Syk signaling cascade. The abnormal activation of B-cell receptor signaling is closely related to the development of B-cell type hematological cancers, which represent approximately 85% of all NHL cases. Therefore, PI3Kδ is considered to be a promising target for drugs that aim to prevent or treat hematologic cancer.
FL accounts for approximately 17% of NHL and MZL accounts for approximately 8% of NHL. In the U.S., there were estimated 13,000 and 6,000 new cases of FL and MZL in 2020, respectively. In China, there were estimated 16,000 and 7,000 new cases of FL and MZL in 2020, respectively 1,2,3.
About HMPL-689
HMPL-689 is a novel, selective and potent oral inhibitor targeting the isoform PI3Kδ. HMPL-689’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, HMPL-689 has the potential to demonstrate an optimal benefit-risk profile in this class.
HUTCHMED has initiated an extensive, globally-focused clinical development pathway for HMPL-689. In addition to the currently Phase II trial and the supportive Phase I trial in China, HMPL-689 is also being evaluated in an ongoing Phase I/Ib study in the U.S. and Europe in patients with relapsed or refractory NHL.
HUTCHMED currently retains all rights to HMPL-689 worldwide.