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BeiGene Presents Clinical Data for BTK Inhibitor BGB-3111 at 57th ASH Annual Meeting

BEIJING, Dec. 7, 2015 (GLOBE NEWSWIRE) -- BeiGene, Ltd., a clinical-stage biopharmaceutical company focused on developing molecularly-targeted and immuno-oncology drugs for the treatment of cancer, today announced that the initial clinical data from an ongoing phase 1 study of BGB-3111 in patients with advanced B cell malignancies were presented at the 57th American Society of Hematology (ASH) annual meeting held in Orlando, FL, December 5-8, 2015. BGB-3111 is a potent and highly selective small molecule inhibitor of Bruton's tyrosine kinase (BTK). The preliminary data show that BGB-3111 is well tolerated and demonstrates single-agent activity in a range of B cell malignancy subtypes.

"BGB-3111 has demonstrated complete and sustained BTK inhibition in circulating and nodal lymphocytes with a favorable tolerability and safety profile. It has produced rapid and durable responses as a monotherapy in different types of B-cell malignancies," commented Constantine Tam, MD, Consultant Haematologist at Peter MacCallum Cancer Centre, Australia, coordinating principal investigator of the study.

"We are very encouraged by the initial clinical data on BGB-3111. We believe BGB-3111's emerging profile is promising and we look forward to further data analysis from the ongoing dose-expansion phase in 2016. In addition, we are initiating more clinical studies in combination with other agents in a variety of B cell malignancies," commented Ruirong Yuan, MD, Chief Medical Officer and President of Global Clinical Development for BeiGene.

The first-in-human multi-center, open-label phase 1 trial of BGB-3111 as monotherapy is being conducted in Australia and New Zealand and is comprised of two parts – a dose-escalation phase involving 25 patients and a dose-expansion phase, in which we plan to enroll a total of 100 patients. The data presented at ASH as an oral presentation (Abstract 832) were from a total of 39 patients, including all 25 patients from the initial dose-escalation component and 14 patients from the ongoing dose-expansion component who were enrolled before August 1, 2015.

No dose limiting toxicities (DLT) were encountered, and the maximum tolerated dose (MTD) was not reached. BGB-3111 achieved high plasma exposure and complete and sustained BTK inhibition in both circulating and nodal lymphocytes.

Based on the pharmacokinetics, pharmacodynamics, safety and efficacy of BGB-3111 in the dose-escalation phase, 320mg once daily and 160 mg twice daily are being further explored in the ongoing dose-expansion trial.

As of October 19, 2015, the cutoff date for data analysis, 29 objective responses have been observed, including 3 complete responses (CRs), 1 very good partial response (VGPR), and 25 partial responses (PRs). Responses by histology are summarized in the table below. 31 of the 39 patients remain on study treatment, free of progression, including all patients to date who have achieved an objective response.

Follow-up Days Best Response ORR
Median (Range) CR PR SD PD (CR + PR)
Chronic
Lymphocytic
Leukemia
220 (83-329) 0/14
(0%)
13/141
(93%)
1/14
(7%)
0
(0%)
13/14
(93%)
Mantle Cell
Lymphoma
148 (84-392) 2/10
(20%)
6/10
(60%)
1/10
(10%)
1/10
(10%)
8/10
(80%)
Waldenström's
Macroglobulinemia
271 (11-398) 0/7
(0%)
6/72
(86%)
0/7
(0%)
1/7
(14%)
6/7
(86%)
DLBCL
29 (20-236) 1/4
(25%)
0/4
(0%)
0/4
(0%)
3/4
(75%)
1/4
(25%)
Indolent
NHL
233 (215-250) 0/2
(0%)
0/2
(0%)
2/2
(100%)
0/2
(0%)
0/2
(0%)
Hairy Cell
Leukemia
362 0/1
(0%)
1/1
(100%)
0/1
(0%)
0/1
(0%)
1/1
(100%)
Burkitt's-like
Lymphoma
84 0/1
(0%)
0/1
(0%)
0/1
(0%)
1/1
(100%)
0/1
(0%)

1 Includes five patients with lymphocytosis at latest assessment; 2 Includes one patient with VGPR

Note: CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; ORR = objective response rate

Eight patients discontinued BGB-3111, including six due to disease progression and two due to adverse events related to their underlying malignancy. Three patients died during study as a result of disease progression or complications of disease progression. There were no drug-related serious adverse events (SAEs). The vast majority of adverse events, regardless of relationship to treatment, were Grade 1 or 2 in severity and not treatment-limiting. Of the 19 ≥Grade 3 AEs, four were assessed by investigators as possibly drug-related – all were self-limited neutropenia, not requiring treatment discontinuation. There was one case of major hemorrhage, defined as a bleeding event grade 3 or higher or an intracranial bleeding event of any grade: GI hemorrhage in a mantle cell lymphoma patient with lymphomatous involvement of the GI tract; this bleeding event occurred during drug hold, and resolved rapidly with re-initiation of BGB-3111 treatment, and therefore is not considered to be drug-related. Six patients had a baseline history of atrial fibrillation/flutter (AF), and no exacerbation or new event of AF was reported.

About BTK and Inhibitors

Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, is a signaling molecule positioned within the B-cell receptor signaling cascade. BTK is predominantly expressed in B lymphocytes at various stages of development. Activation of BTK in B cells initiates a series of signaling events that leads to subsequent NF-κB activation and the expression of genes involved in proliferation and survival. Clinically, BTK inhibitors have demonstrated antitumor responses as a single agent in patients with B-cell malignancies.

About BGB-3111

BGB-3111 is a potent and highly selective small molecule BTK inhibitor. BGB-3111 has demonstrated higher selectivity against BTK than ibrutinib, the only BTK inhibitor currently approved by the U.S. Food and Drug Administration, or FDA, and the European Medicines Agency, or EMA. BGB-3111 is an orally active inhibitor of BTK that covalently binds to the cysteine Cys-481 of BTK, resulting in irreversible inactivation of the kinase. Nine other kinases in the human genome, including ITK, EGFR and JAK3, contain this similar cysteine residue, however BGB-3111 has been shown to be selective against the BTK.

About BeiGene

BeiGene is a global, clinical-stage, research-based biotechnology company focused on targeted and immuno-oncology therapeutics. With a team of 190+ scientists and staff, BeiGene is advancing a pipeline consisting of novel oral small molecules and monoclonal antibodies for cancer. BeiGene is working to create combination solutions aimed to have both a meaningful and lasting impact on cancer patients. For more information, please visit our website at www.beigene.com.

CONTACT: Media/Investor Contact: Xin Huang US: +1 917-617-4653 China: +86 185-1406-3050 pr@beigene.com

Source:BeiGene Ltd.