吉利德GS-9973 II期CLL中期分析取得积极数据

吉利德（Gilead）12月7日公布了实验性化合物GS-9973的一项II期研究的中期数据。GS-9973是一种实验性口服脾酪氨酸激酶（spleen tyrosine kinase，Syk）抑制剂，在该项研究中，用于复发或难治性慢性淋巴细胞白血病（CLL）的治疗。数据表明，接受GS-9973单药疗法至少8周的CLL患者组，97%的患者经历了淋巴结体积的缩小。

目前，大多数CLL患者最终会对当前疗法产生抗性。这一现状表明，寻找新的可用于CLL患者治疗的药物，具有无比的重要性。B细胞受体信号通路是寻找实验性药物治疗CLL的新兴领域。GS-9973靶向于Syk蛋白，该蛋白启动来自于B细胞受体的大部分信号。

该项研究中期分析中所观察到的响应率，表明GS-9973在CLL中具有非常有前途的临床治疗活性，值得进一步的探索和开发。

在疗效分析所涉及的29例CLL患者中，69%的患者取得了超过50%的肿瘤收缩，其中包括4例携带染色体17p缺失和/或TP53基因突变的患者，这些基因异常已与较差的预后相关联。

关于GS-9973：

GS-9973是一种实验性、靶向性、可逆性口服脾脏酪氨酸激酶（Syk）抑制剂，Syk是一种蛋白，对于B细胞的活化、增殖和生存至关重要。目前，吉利德正在一项II期研究中，评价GS-9973与idelalisib组合疗法，用于复发或难治性慢性淋巴细胞白血病（CLL）、惰性非霍奇金淋巴瘤（iNHL）、以及其他淋巴和血液系统恶性肿瘤的治疗。

idelalisib是一种实验性、高度选择性、口服有效的磷酸肌醇3-激酶delta（PI3K-delta）抑制剂。PI3K-delta信号对于B淋巴细胞的活化、增殖、生存、迁移（trafficking）至关重要，该信号在多种B细胞恶性肿瘤中过度活动。目前，idelalisib正被开发作为单一制剂，以及与一些已获批的疗法和实验性疗法配伍。

英文原文：Gilead Announces Interim Phase 2 Results for GS-9973 in Previously Treated Chronic Lymphocytic Leukemia

-- Data Presented at the 55th American Society of Hematology Annual Meeting --

NEW ORLEANS--(BUSINESS WIRE)--Dec. 7, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced interim results from a single-arm, open-label Phase 2 study evaluating GS-9973, an investigational oral inhibitor of spleen tyrosine kinase (Syk), for the treatment of patients with relapsed or refractory hematologic malignancies. The data show that among patients with chronic lymphocytic leukemia (CLL) who received at least eight weeks of GS-9973 monotherapy, 97 percent (n=28/29) experienced a reduction in lymph node size. Detailed results will be presented today during a poster session at the 55th Annual Meeting of the American Society of Hematology (ASH) in New Orleans (Abstract #1634).

“Most patients with CLL eventually develop resistance to currently available therapies,” said Jeff Sharman, MD, Willamette Valley Cancer Institute and Research Center – River Bend. “This underscores the importance of identifying new treatments for patients with CLL. The B cell receptor signaling pathway is a novel area of focus for investigational therapies in CLL. GS-9973 targets the Syk protein, which initiates most signaling from the B cell receptor. Response rates observed in this interim analysis support that GS-9973 has promising clinical activity in CLL to be further explored and developed.”

Of the 29 CLL patients included in the efficacy analysis, 20 (69 percent) achieved greater than 50 percent tumor shrinkage, including four of seven patients with a chromosome 17p deletion and/or a mutation in the TP53 gene, genetic abnormalities that have been linked to poor prognosis.

The safety of GS-9973 was also assessed in a population of 78 patients with CLL or non-Hodgkin’s lymphoma (NHL) who had received at least four weeks of therapy. At the time of the data cut-off, 50 patients (64 percent) were continuing with GS-9973 treatment, with a median exposure of 10 weeks (range: 1-24 weeks).

Among the 78 patients in the safety analysis, five (six percent) reported Grade ≥3 fatigue. Reversible Grade ≥3 transaminase elevations (a measure of liver function) were reported in nine patients (12 percent). Eleven patients (14 percent) discontinued treatment due to adverse events. Four patients died during the study, three from progressive disease and one from septic shock.

About the Study

This Phase 2, open-label, single-arm safety and efficacy study is evaluating GS-9973 (800 mg twice daily) in patients with relapsed or refractory CLL or NHL, including indolent NHL (iNHL), diffuse large B-cell lymphoma and mantle cell lymphoma. The median age of the patients included in the safety analysis presented today was 72 years. These patients had received a median of two prior treatment regimens before study entry. The primary endpoint of the study is progression-free survival. Patients are allowed to continue daily dosing as long as they benefit from therapy. At the time of the data cut-off, it was too early to quantitate drug activity in the NHL population. The study is ongoing.

About GS-9973

GS-9973 is an investigational, targeted, reversible oral inhibitor of spleen tyrosine kinase (Syk), a protein that is critical for the activation, proliferation and survival of B lymphocytes. Combination therapy with GS-9973 and idelalisib, Gilead’s investigational, targeted, oral inhibitor of PI3K delta, is also being evaluated in a Phase 2 trial of patients with relapsed or refractory CLL, iNHL and other lymphoid and hematological malignancies.

GS-9973 and idelalisib are investigational products and their safety and efficacy have not been established.

About Chronic Lymphocytic Leukemia

CLL is a slow-growing cancer in which the bone marrow overproduces white blood cells, leaving less room in the blood and bone marrow for other types of blood cells. It is the most common leukemia in adults in the United States, occurring typically in older individuals, and it can lead to life-threatening complications, including serious infections and anemia. In 2013, there were an estimated 16,000 new CLL diagnoses in the United States and 4,500 deaths related to this cancer.)