A PHASE I STUDY OF THE BTK INHIBITOR ABIVERTINIB (AC0010) IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL LYMPHOMA
Author(s): ,
Min Yang
Affiliations:
Department of Hematology,The First Affiliated Hospital, Zhejiang University School of Medicine,Hangzhou,China
,
Jiejing Qian
Affiliations:
Department of Hematology,The First Affiliated Hospital, Zhejiang University School of Medicine,Hangzhou,China
,
Jiansong Huang
Affiliations:
Department of Hematology,The First Affiliated Hospital, Zhejiang University School of Medicine,Hangzhou,China
,
Ying Jiao
Affiliations:
Department of Global Clinical Development,ACEA Pharmaceutical Research,Beijing,China
,
Wei Tang
Affiliations:
Discovery Biology,ACEA Pharmaceutical Research,Hangzhou,China
,
Xiao Xu
Affiliations:
CEO,ACEA Pharmaceutical Research,Hangzhou,China
,
Wanhong Xu
Affiliations:
GM,ACEA Pharmaceutical Research,Hangzhou,China
,
Feng Roger Luo
Affiliations:
Department of Global Clinical Development,ACEA Therapeutics Inc.,San Diego,United States
Jie Jin
Affiliations:
Department of Hematology,The First Affiliated Hospital, Zhejiang University School of Medicine,Hangzhou,China
EHA Library. Yang M. Jun 14, 2019; 266315; PF515
Min Yang
Min Yang
Contributions
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Abstract

Abstract: PF515

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
Bruton’s tyrosine kinase (BTK) is a clinically validated target for the treatment of B-cell malignancies, including relapsed/refractory (R/R) mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), and Waldenström’s macroglobulinemia (WM). Abivertinib is a highly selective, irreversible, potent inhibitor of BTK activity, which is being investigated in an open-label phase I study with dose escalation (part 1) and dose expansion (part 2) (NCT03060850).

Aims
This ongoing study is designed to determine the recommended Phase 2 dose (RP2D) of abivertinib in patients with pre-treated R/R B-cell lymphoma (part 1) and to evaluate the safety and preliminary efficacy in patients with selected disease (part 2).

Methods
In part 1, eligible patients aged 18-75 y, with Eastern Cooperative Oncology Group performance status of 0 or 1, and diagnosed with R/R B-cell lymphoma were enrolled. Patients received abivertinib until progressive disease or unacceptable toxicity. The primary endpoint of part 1 is to determine RP2D based on dose limited toxicity (DLT), adverse event (AE), tolerability, BTK receptor occupancy, pharmacokinetics and preliminary efficacy. Abivertinib was given twice a day (BID) or once a day in 28-day treatment cycles in ascending/descending dose cohorts, the starting dose was 200mg BID. Here, we report the preliminary safety and efficacy outcomes in part 1, and part 2 will be initiated upon determinate of RP2D.

Results
As of November 15, 2018, 21 patients with R/R B-cell malignancy were enrolled for treatment in part 1, including CLL (n=9), SLL (n=1), MZL (n=1), MCL (n=5), follicular lymphoma (n=1), lymphoplasmacytic lymphoma (n=3), mucosa-associated lymphoid tissue (n=1). Patients received treatment with abivertinib in 3 dose cohorts (300mg BID, n=3; 200mg BID, n=14; 150mg BID, n=4). The median treatment duration was 27 (range 1-85) weeks; 66.9% (14/21) of patients are still on treatment. Three (14.3%) DLT events of platelet count decrease were reported, 1 at 300mg BID and 2 at 200mg BID. Overall, treatment emergent AE occurred in 85.7% (18/21) of patients, with 47.6% (10/21) of grade 3/4 AE. The most common grade 3/4 AE regardless of causality (>10%) was thrombocytopenia (4/21, 19.0%), followed by neutropenia (3/21, 14.3%). Treatment emergent serious adverse event (SAE) occurred in 23.8% (5/21) of patients, only 1 case (4.8%) of drug-related SAE abdominal infection was reported. No death occurred during the treatment period. The efficacy was analyzed in the 13 response evaluable patients, 61.5% (8/13) of patients achieved partial response (PR) across 3 dose cohorts and 87.5% (7/8) of patients achieved PR at 200mg BID. Furthermore, >90% BTK occupancy in peripheral blood was achieved at all 3 dose levels.

Conclusion
Abivertinib was safe and tolerable with encouraging clinical efficacy in patients with R/R B-cell malignancies, which warrants further evaluation in part 2 of the study.

Session topic: 20. Lymphoma Biology & Translational Research

Keyword(s): B cell lymphoma, Phase I

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