百济神州公布淋巴瘤新药、BTK抑制剂BGB-3111的最新临床试验结果

药时代热烈祝贺百济神州！

（图片来源：ICML官网）

百济神州参加了2017年6月14日至17日在瑞士卢加诺举行的第14届国际恶性淋巴瘤会议（14-ICML），公布了其BTK（Bruton's酪氨酸激酶）抑制剂BGB-3111与抗CD20抗体奥比妥珠单抗（obinutuzumab）联合用药的临床1期试验的初步数据。

试验针对的适应症有慢性淋巴细胞白血病（CLL）、小淋巴细胞性淋巴瘤（SLL）和滤泡淋巴瘤（FL）。数据表明：

• 组合药物显示良好的耐受

• 在初治CLL / SLL患者中的总体缓解率（ORR）为89％，其中22％的完全缓解率（CRs）

• 在复发/难治性（R / R）CLL / SLL患者中的ORR为92％，CR为16％

• 在复发/难治性FL患者中ORR为73%，CR为33％

BGB-3111是一个处于临床研究阶段的强效高选择性的BTK小分子抑制剂。 基于生物化学分析，BGB-3111已经显示出比依鲁替尼更高的选择性；基于各自的I期临床试验数据，BGB-3111有更高的暴露量，在血液和淋巴结中BTK occupancy可维持24小时。依鲁替尼（Ibrutinib）是目前唯一一个被美国食品药品监督管理局（FDA）和欧洲药物管理局（EMA）批准的BTK抑制剂。

百济神州还宣布计划对BGB-3111开展更多全球注册试验。

关于奥比妥珠单抗：

Obinutuzumab（2009年之前被称为阿托单抗（afutuzumab），最开始的代号为GA101）是人源化的抗CD20单克隆抗体，是由GlycArt Biotechnology AG公司首创、由罗氏（Roche）旗下的基因泰克（Genentech）开发的癌症治疗药物。 它于2013年被美国FDA批准，商业名称为Gazyva，获得欧盟EMA批准，商品名Gazyvaro，与化疗联合治疗慢性淋巴细胞性白血病初治患者，同时作为滤泡性淋巴瘤的二线治疗。作为第二代anti-CD20单抗，生存期方面优于第一代的利妥昔单抗。

关于国际恶性淋巴瘤会议：

自1981年举办第一届会议以来，国际恶性淋巴瘤会议（The International Conference on Malignant Lymphoma，ICML）已成为参与淋巴瘤研究和治疗的科学界必须参加的活动。

了解详情，请阅读下面转载的百济神州新闻稿。

BeiGene Presents Initial Phase 1 Data on BTK Inhibitor BGB-3111 Combined with Obinutuzumab at the 14th International Conference on Malignant Lymphoma and Announces Additional Planned Global Registrational Trials for BGB-3111

CAMBRIDGE, Mass. and BEIJING, China, June 16, 2017 (GLOBE NEWSWIRE) -- BeiGene, Ltd.(NASDAQ:BGNE), a clinical-stage biopharmaceutical company developing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, today presented initial clinical data from an ongoing Phase 1 trial of the Bruton’s Tyrosine Kinase (BTK) inhibitor BGB-3111 combined with the anti-CD20 antibody obinutuzumab in patients with chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) and follicular lymphoma (FL) at the 14th International Conference on Malignant Lymphoma (14-ICML) in Lugano, Switzerland. The initial Phase 1 data demonstrate that the combination is well tolerated with an overall response rate (ORR) of 89% including complete responses (CRs) in 22% of treatment naïve (TN) CLL/SLL patients, an ORR of 92% with CRs in 16% of relapsed/refractory (R/R) CLL/SLL patients, and an ORR of 73% with CRs in 33% of R/R FL patients.

“This clinical trial is supported by preclinical work suggesting that BGB-3111 may combine well with antibodies that rely on antibody-dependent cell-mediated cytotoxicity, such as obinutuzumab, because of less off-target inhibition of interleukin-2-inducible T-cell kinase. The preliminary clinical results to date suggest that the combination is well tolerated and highly active in patients with CLL or SLL and FL. Complete responses have already been observed in patients with both disease types, including CLL or SLL patients with high-risk features, despite a very short follow-up time,” commented Constantine Tam, MD, Disease Group Lead for Low Grade Lymphoma and Chronic Lymphocytic Leukemia at Peter MacCallum Cancer Centre, Director of Haematology at St. Vincent’s Hospital, Australia, and lead author of the presentation.

“We are very pleased to report initial results from our first combination trial with BGB-3111. The preliminary complete response rate in CLL and SLL, as well as the frequency and depth of responses in FL, appear to be favorable compared to reported data with BTK inhibitors or anti-CD20 antibodies alone. Given the depth and durability of BGB-3111 monotherapy activity in our trials to date, we look forward to seeing the combination data mature over time and plan to initiate late-stage trials of this combination in FL,” commented Jane Huang, MD, Chief Medical Officer, Hematology at BeiGene.

On the basis of data presented on BGB-3111, BeiGene announced that it plans to expand its global registrational program for BGB-3111 to include a Phase 2 pivotal trial of BGB-3111 in combination with obinutuzumab compared to obinutuzumab alone in patients with R/R FL. In addition, based on data with BGB-3111 monotherapy presented earlier at this meeting, BeiGene is planning to initiate a Phase III trial comparing BGB-3111 with bendamustine plus rituximab in patients with TN CLL. These two additional trials will expand the late-stage clinical trial program for BGB-3111, which includes an ongoing global Phase 3 comparison trial with ibrutinib in Waldenström’s macroglobulinemia (WM) and single-arm pivotal trials in R/R CLL/SLL and R/R mantle cell lymphoma intended to support approval of BGB-3111 in China. 

Summary of Results from the Ongoing Phase 1 Trial

The multi-center, open-label Phase 1 trial of BGB-3111 with obinutuzumab in patients with B-cell malignancies is being conducted in Australia and the United States and consists of a dose-escalation phase and a dose-expansion phase in disease-specific cohorts, which include TN or R/R CLL/SLL and R/R FL. The dose-escalation component is testing BGB-3111 at 320 mg once daily (QD) or 160 mg twice daily (BID) in 28-day cycles, in combination with obinutuzumab; obinutuzumab was administered in line with standard CLL dosing (three loading doses of 1000 mg weekly followed by 1000 mg on day one of cycles 2–6). The ongoing dose-expansion component is testing doses of BGB-3111 at 160 mg BID with the same obinutuzumab schedule. As of March 31, 2017, 45 patients with CLL/SLL and 17 patients with FL were enrolled in the trial.

At the time of the data cutoff of March 31, 2017, BGB-3111 was shown to be well tolerated in both CLL/SLL and FL. The most frequent adverse events (AEs) (≥15%) of any attribution in CLL/SLL were petechiae/purpura/contusion (33%), neutropenia (31%), thrombocytopenia (22%), fatigue (18%), pyrexia (18%), upper respiratory tract infection (18%), and diarrhea (16%); all of these were grade 1 or 2 except for grade 3 or 4 neutropenia (20%) and grade 3 or 4 thrombocytopenia (4%). The most frequent AEs (≥15%) in FL were petechiae/purpura/contusion (35%), fatigue (29%), cough (18%), diarrhea (18%), dizziness (18%), headache (18%), insomnia (18%), nausea (18%), and upper respiratory tract infection (18%); all of these were grade 1 or 2. Serious AEs occurred in 24% of both the CLL/SLL and FL patients. Infusion-related reactions occurred in 24% of CLL/SLL patients and 6% of FL patients; all cases were grade 1 or 2 except for one grade 4 case in a CLL/SLL patient. There were no cases of serious hemorrhage (≥ grade 3 hemorrhage or central nervous system hemorrhage of any grade) or atrial fibrillation. Only one patient discontinued treatment due to an AE, squamous cell carcinoma (SCC), and this patient had a prior history of SCC.

At the time of the data cutoff, 43 patients with CLL/SLL (18 TN, 25 R/R) and 15 patients with R/R FL had greater than 12 weeks of follow-up and were evaluable for efficacy. In TN CLL/SLL, after a median follow-up of 7.0 months (2.8–11.8 months), the overall response rate (ORR) was 89% with complete responses (CRs) in 22% and partial responses (PRs) in 67% of patients. Stable disease (SD) was observed in 11% of patients. In R/R CLL/SLL, at a median follow-up time of 8.0 months (3.8–14.0 months) the ORR was 92% with CRs in 16% and PRs in 76% of patients. SD was observed in 4% of patients. In R/R FL, at a median follow-up time of 6.2 months (1.2–10.7 months), the ORR was 73% with CRs in 33% and PRs in 40% of patients. Stable disease was observed in 13% of patients. One patient with R/R CLL/SLL had progressive disease (Richter’s transformation), and two patients with R/R FL had progressive disease.

Investor Call and Webcast Information

BeiGene will host an investor call and webcast to discuss the data presented at 14-ICML and its development program.

Date & Time: Friday, June 16, 2017, 2:00 PM CEST (8:00 AM EDT, 8:00 PM China Standard Time)

Dial-in Numbers: 1-845-675-0437 or 1-866-519-4004 (US), 400-620-8038 or 800-819-0121 (China), [phone] (Hong Kong), or [phone] (International)

Conference ID Number: 33044427

A live webcast and replay will be available on BeiGene’s investor website http://ir.beigene.com/. The dial-in replay will be available approximately two hours after the conference and will be available for two days following the event. It can be accessed by dialing 1-646-254-3697 (US), 400-632-2162 (China), [phone] (Hong Kong), or [phone] (International).

About BGB-3111

BGB-3111 is a potent and highly selective investigational small molecule inhibitor of BTK (Bruton’s Tyrosine Kinase). BGB-3111 has demonstrated higher selectivity against BTK than ibrutinib (the only BTK inhibitor currently approved by the U.S. Food and Drug Administrationand the European Medicines Agency) based on biochemical assays, higher exposure than ibrutinib based on their respective Phase I experience, and sustained 24-hour BTK occupancy in both the blood and the lymph node.

About BeiGene

BeiGene is a global, clinical-stage, research-based biotechnology company focused on molecularly targeted and immuno-oncology cancer therapeutics. With a team of over 400 employees in China, the United States, and Australia, BeiGene is advancing a pipeline consisting of novel oral small molecules and monoclonal antibodies for the treatment of cancer. BeiGene is working to create combination solutions aimed at having both a meaningful and lasting impact on cancer patients.

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