amdizalisib (HMPL-689) / Hutchmed - LARVOL DELTA

Tazemetostat plus Amdizalisib in Relapsed/Refractory Peripheral T–cell Lymphoma Patients with Diverse Genomic Signatures: Results from a Phase 2 Study (ICML 2025) - No abstract available

Clinical • P2 data • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Clinical Study of HMPL-689 for Relapsed/Refractory Marginal Zone Lymphoma and Follicular Lymphoma (clinicaltrials.gov) - P2 | N=178 | Completed | Sponsor: Hutchison Medipharma Limited | Recruiting ➔ Completed

Trial completion • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

A Study of Tazemetostat in Combination With HMPL-689 in Patients With Relapsed/Refractory Lymphoma (clinicaltrials.gov) - P2 | N=61 | Completed | Sponsor: Hutchmed | Recruiting ➔ Completed | N=140 ➔ 61 | Trial completion date: Dec 2026 ➔ Dec 2024 | Trial primary completion date: May 2026 ➔ Dec 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma

Mass balance, metabolism, and pharmacokinetics of [14C]amdizalisib, a clinical-stage novel oral selective PI3Kδ inhibitor for the treatment of non-hodgkin's lymphoma, in healthy Chinese volunteers. (PubMed, Front Pharmacol) - "These findings demonstrate that amdizalisib is rapidly absorbed, extensively metabolized, and primarily excreted via feces and urine, supporting its continued development as a potential therapeutic for Hodgkin's lymphoma. https://www.chinadrugtrials.org.cn/, identifier CTR20212448."

Journal • PK/PD data • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PIK3CD

Preclinical pharmacokinetic characterization of amdizalisib, a novel PI3Kδ inhibitor for the treatment of hematological malignancies. (PubMed, Front Pharmacol) - "It exhibited induction potential on CYP1A2, CYP2B6, CYP3A4, and CYP2C9. The preclinical data from these ADME studies demonstrate a favorable pharmacokinetic profile for amdizalisib, which is expected to support the future clinical development of amdizalisib as a promising anti-cancer agent."

Journal • PK/PD data • Preclinical • Breast Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • CYP1A2 • CYP2C9 • CYP3A4 • PIK3CD

PHASE II STUDY OF EZH2 INHIBITOR TAZEMETOSTAT PLUS AMDIZALISIB, A PI3K INHIBITOR, IN PATIENTS WITH RELAPSED/REFRACTORY LYMPHOMAS (EHA 2024) - "The combination of amdizalisib and TAZ showed promising efficacy with manageable safety profile in R/Rlymphoma, especially in PTCL and DLBCL. However, larger sample and long-term follow-up are needed tofurther validate efficacy and safety."

Clinical • P2 data • Anemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • CYP3A4 • PIK3CD

Preclinical pharmacokinetic characterization of amdizalisib, a novel PI3Kδ inhibitor for the treatment of hematological malignancies (Front Pharmacol) - "Amdizalisib was extensively metabolized in vivo, and the recovery rate of the prototype drug was low in the excreta. Amdizalisib and/or its metabolites were primarily excreted via the bile and urine in rats. Amdizalisib showed inhibition potential on P-gp but not on BCRP and was observed to inhibit CYP2C8 and CYP2C9 with IC50 values of 30.4 and 10.7 μM, respectively."

Preclinical • Hematological Malignancies

Number of figures: 3 Number of tables: 8 Preclinical pharmacokinetics characterization of Amdizalisib, a novel PI3Kδ inhibitor for treatment of hematological malignancies (Front Oncol) - "Amdizalisib and/or its metabolites were primarily excreted via the bile and urine in rats. Amdizalisib showed inhibition potential on P-gp, but not on BCRP, and was observed to inhibit CYP2C8 and CYP2C9 with IC50 values of 30.4 and 10.7 μM, respectively. It exhibited the induction potential on CYP1A2, CYP2B6, CYP3A4 and CYP2C9."

Preclinical • Hematological Malignancies

Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas (clinicaltrials.gov) - P1 | N=53 | Active, not recruiting | Sponsor: Hutchmed | Trial completion date: Aug 2023 ➔ Dec 2024 | Trial primary completion date: Aug 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Oncology

A Study of HMPL-689 in Patients With Lymphomas Failed of Standard of Care or no Standard of Care Existed (clinicaltrials.gov) - P1 | N=200 | Completed | Sponsor: Hutchison Medipharma Limited | Active, not recruiting ➔ Completed

Trial completion • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma

HUTCHMED Reports 2023 Interim Results and Provides Business Updates (GlobeNewswire) - "Potential upcoming clinical and regulatory milestones for amdizalisib: Report top-line results from the China registration Phase II study for the treatment of follicular lymphoma in late 2023....Potential upcoming clinical and regulatory milestones for tazemetostat: Complete recruitment of a China bridging study in follicular lymphoma for conditional registration based on U.S. approvals in H2 2023 (NCT05467943)."

Enrollment status • P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

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 (ICML 2023) - P1 | "Amdizalisib showed an acceptable safety profile and promising anti-tumor activity in R/R lymphoma, providing evidence for future investigations. Clinical trial information: NCT03128164."

Clinical • P1 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Small Lymphocytic Lymphoma • T Cell Non-Hodgkin Lymphoma • PIK3CD

HUTCHMED Highlights Presentations for Hematological Malignancy Programs at the 2023 EHA and ICML Meetings (GlobeNewswire) - P1b | N=53 | NCT03786926 | Sponsor: Hutchmed | "HUTCHMED...announces 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') 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....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....Median DoR was not reached and median PFS was 26.8 months for the 16 efficacy evaluable patients in the MZL cohort."

P1 data • Acute Myelogenous Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Amdizalisib (HMPL-689), a highly selective PI3Kδ inhibitor, exhibits potent anti-tumor activity in pre-clinical B-cell lymphoma models (AACR 2022) - P2 | "Human B cell lymphoma cell line derived xenograft models were used to determine the anti-tumor activity of Amdiz in combination with other agents such as rituximab, BTK inhibitor, and venetoclax. Amdiz is a highly selective inhibitor of PI3Kδ, showing more than 250-fold selectivity over other PI3K isoforms and no significant inhibition over other 319 protein kinases at the concentration of 1 µM. Amdiz is a highly potent and selective PI3Kδ inhibitor with strong activity against B-cell lymphoma in pre-clinical studies, supporting clinical evaluation as either a single agent or in combination with other therapeutic agents for the treatment of B-cell malignancies."

Preclinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD63 • CD86 • PIK3CD

[VIRTUAL] A Phase 1 Study of HMPL-689, a Small Molecule, Highly Selective, and Potent Inhibitor of Phosphoinositide 3 Kinase-Delta, in Patients with Relapsed or Refractory Lymphoma (ASH 2020) - P1 | "Continuous assessments will be summarized by number of patients (n), mean, standard deviation, median, minimum and maximum. Significance: This study is the first global clinical study of HMPL-689, a novel inhibitor of the BCR signaling pathway, which is currently enrolling patients with advanced relapsed, refractory, or resistant NHL who have exhausted all approved therapeutics options available."

Clinical • P1 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

HUTCHMED Reports 2022 Full Year Results and Provides Business Updates (HUTCHMED Press release) - "Potential upcoming clinical and regulatory milestones for surufatinib: Complete bridging study in NET patients in Japan (NCT05077384) in the first half of 2023 and discuss results with the Japanese PMDA....Potential upcoming clinical and regulatory milestones for amdizalisib: Report top-line results from the China registration Phase II study for the treatment of follicular lymphoma in H2 2023."

P1/2 data • P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Neuroendocrine Tumor • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

HUTCHMED Completes Patient Enrollment of Phase II Registration Trial of Amdizalisib in Follicular Lymphoma in China (GlobeNewswire) - "HUTCHMED (China) Limited...announces that it has completed patient enrollment of Phase II registration trial of amdizalisib in patients with relapsed or refractory follicular lymphoma ('FL'), a subtype of non-Hodgkin’s lymphoma ('NHL'). The last patient was enrolled on February 24, 2023....Topline results on the FL patients in this trial are expected to be reported in the second half of 2023, followed by submission of results for presentation at an appropriate medical conference. If positive, HUTCHMED would initiate plans to apply for marketing authorization of amdizalisib for relapsed/refractory FL from the China National Medical Products Administration (NMPA)."

Non-US regulatory • P2 data • Trial status • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of Tazemetostat in Combination With HMPL-689 in Patients With Relapsed/Refractory Lymphoma (clinicaltrials.gov) - P2 | N=140 | Recruiting | Sponsor: Hutchmed | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma

A Study of Tazemetostat in Combination With HMPL-689 in Patients With Relapsed/Refractory Lymphoma (clinicaltrials.gov) - P2 | N=140 | Not yet recruiting | Sponsor: Hutchmed

Combination therapy • New P2 trial • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma

Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas (clinicaltrials.gov) - P1 | N=53 | Active, not recruiting | Sponsor: Hutchmed | Recruiting ➔ Active, not recruiting | N=270 ➔ 53

Enrollment change • Enrollment closed • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

HMPL-689 Drug Interaction Study With CYP3A Inhibitor/CYP2C9 Inhibitor/CYP3A Inducer/PPI (clinicaltrials.gov) - P1 | N=59 | Completed | Sponsor: Hutchmed

New P1 trial

Effect of a high-fat meal on the relative bioavailability of HMPL-689 in Chinese Healthy Volunteers. (PubMed, Fundam Clin Pharmacol) - "The study indicated that intake of a high-fat diet had an impact on the in vivo PK profile of HMPL-689 in healthy Chinese male subjects, which could obviously reduce the oral absorption rate of HMPL-689 and had little effect on the extent of oral absorption (AUC)."

Journal

A Study of HMPL-689 in Patients With Lymphomas Failed of Standard of Care or no Standard of Care Existed (clinicaltrials.gov) - P1 | N=200 | Active, not recruiting | Sponsor: Hutchison Medipharma Limited | Unknown status ➔ Active, not recruiting | N=83 ➔ 200 | Trial completion date: Jul 2021 ➔ Sep 2023 | Trial primary completion date: Jul 2020 ➔ Aug 2023

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma

HUTCHMED Reports 2022 Interim Results and Provides Business Updates (GlobeNewswire) - "Potential upcoming clinical and regulatory milestones for amdizalisib: Plan for additional Phase II studies with potential for registration intent in China in additional relapsed/​refractory lymphoma indications; Initiate studies in combination with tazemetostat and other anti-cancer therapies in China; and Complete recruitment of patients for two Phase II studies with potential for registration in China for the treatment of follicular lymphoma (with Breakthrough Therapy Designation) around the end of 2022 and marginal zone lymphoma in the first half of 2023 (NCT04849351)....Potential upcoming clinical milestones for sovleplenib: Complete enrollment of the ESLIM-01 Phase III pivotal study in primary ITP (NCT03951623) in China around year end, with readout in 2023; Initiate Phase I study in the U.S. in patients with ITP in 2023."

Enrollment status • New P1 trial • New P2 trial • New trial • Trial status • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

HUTCHMED Reports 2021 Full Year Results and Provides Business Updates (GlobeNewswire) - "Potential upcoming clinical and regulatory milestones for amdizalisib in 2022: Initiate additional Phase II studies with potential for registration intent in China in additional relapsed/refractory non-Hodgkin’s lymphoma indications in the second half of 2022; Initiate studies in combination with other anti-cancer therapies in China in early 2022; and Complete recruitment of patients for Phase II studies with potential for registration intent in China for the treatment of follicular lymphoma and marginal zone lymphoma in late 2022."

New P2 trial • New trial • Follicular Lymphoma • Hematological Malignancies • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology