The 65th Annual Meeting of the American Society of Hematology (ASH) took place from December 9th to 12th, 2023, in San Diego, USA. HeaZen Therapeutics's independently developed new generation BTK inhibitor, HZ-A-018, and the dual-target CK1ε/PI3Kδ inhibitor, HZ-H08905, presented their latest clinical research data at the conference through posters. The research covered areas such as B-cell lymphoma and T/NK-cell lymphoma, with the full abstracts available on the ASH official website.

BTK Inhibitor HZ-A-018:

Publication Number: 3139

Title: A Phase I/II Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of BTK Inhibitor HZ-A-018 in Adult Patients with Relapsed and/or Refractory Central Nervous System Lymphoma

Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster II

Date and Time (US Time): December 10, 2023, Sunday, 18:00-20:00

Summary:

1.HZ-A-018 is a highly selective and potent covalent BTK inhibitor with high blood-brain barrier penetration. Currently, a Phase I/II clinical study (CTR20210181) is being conducted in China to investigate the safety/tolerability, pharmacokinetics, and antitumor efficacy of HZ-A-018 in patients with Central Nervous System Lymphoma (CNSL).

2.As of May 30, 2023, a total of 21 patients were enrolled, including 18 with relapsed/refractory primary CNS lymphoma (R/R PCNSL) and 3 with relapsed/refractory secondary CNS lymphoma (R/R SCNSL). All patients had previously received chemotherapy containing HD-MTX.

3.In terms of safety, the most common treatment-related adverse events (TRAEs ≥10%) were thrombocytopenia, neutropenia, leukopenia, and hypokalemia, most of which were Grade 1 or 2.

4.In terms of efficacy, among the 21 evaluable patients, the Overall Response Rate (ORR) was 52.4%, Complete Response Rate (CRR) was 23.8%, and Disease Control Rate (DCR) was 71.4%. In the 600mg dose group, all patients achieved a high response, with an ORR of 100% and a CRR of 50%.

5.Phase I study results indicate that HZ-A-018 has good safety/tolerability and excellent efficacy in PCNSL patients, and there are plans to conduct a pivotal clinical study for R/R PCNSL in China.

Abstract Link: https://ash.confex.com/ash/2023/webprogram/Paper185241.html

CK1ε & PI3Kδ Dual Inhibitor HZ-H08905:

Publication Number: 4428

Title: A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Dual CK1ε/PI3Kδ Inhibitor HZ-H08905 in Adult Patients with Relapsed and/or Refractory Hematologic Malignancies

Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster III

Date and Time (US Time): December 11, 2023, Monday, 18:00-20:00

Summary:

1.HZ-H08905 is a novel, highly selective, and potent dual-target CK1ε&PI3Kδ inhibitor. A multicenter Phase I clinical study (CTR20213233) is currently underway in China to assess the safety/tolerability, pharmacokinetics, and antitumor efficacy of HZ-H08905.

2.As of May 25, 2023, a total of 38 patients were enrolled, including 26 with relapsed/refractory T-cell lymphoma (R/R TCL) and 12 with relapsed/refractory B-cell lymphoma (R/R BCM).

3.In terms of safety, no dose-limiting toxicity (DLT) was observed during the dose-escalation process (50-450mg), and the maximum tolerated dose (MTD) was not reached. Grade ≥3 TRAEs (>5%) included neutropenia, pneumonia, leukopenia, elevated aspartate aminotransferase, elevated alanine aminotransferase, and herpes zoster.

4.In terms of efficacy, among the 35 evaluable patients, the ORR was 60%, and the CRR was 17%; the median duration of response (mDOR) and median progression-free survival (mPFS) were not reached. Preliminary results show that HZ-H08905 exhibits excellent antitumor effects in various subtypes of non-Hodgkin's lymphoma (NHL), including chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL), and Waldenström's macroglobulinemia (WM).

5.Phase I study results indicate that HZ-H08905 has good safety/tolerability and excellent efficacy in NHL patients, and there are plans to conduct a registrational clinical study for R/R PTCL in China.

Abstract Link: https://ash.confex.com/ash/2023/webprogram/Paper185363.html