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Gilead to Present Data on Oncology Pipeline at American Society of Hematology Annual Meeting
-- Presentations Include Updated Results from Trial of Idelalisib for Refractory Indolent Non-Hodgkin’s Lymphoma and First Data for Novel Syk Inhibitor in Chronic Lymphocytic Leukemia --
FOSTER CITY, Calif.--(BUSINESS WIRE)--Nov. 7, 2013-- Gilead Sciences, Inc. (NASDAQ: GILD) today announced that 10 abstracts describing the company's investigational agents for several hematological malignancies have been selected for presentation at the Annual Meeting of the American Society of Hematology (ASH) taking place December 7-10 in New Orleans. The abstracts describe clinical and pre-clinical data from studies of idelalisib, which is currently under review by the U.S. Food and Drug Administration for treatment of refractory indolent non-Hodgkin’s lymphoma (iNHL), as well as for GS-9973, GS-9820 and momelotinib (formerly CYT387 / GS-0387). Detailed results from these studies will be presented at the conference.
- See more at: http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=...
Source: press release, 11/07/13. http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=...
A Phase 2, Open-Label Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacodynamics of GS-9973 in Subjects With Relapsed or Refractory Hematologic Malignancies
Estimated Enrollment: 280
Study Start Date: March 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Source: clinical trials.gov. http://clinicaltrials.gov/ct2/show/NCT01799889?term=GS-9973&rank=1
|GS-9973||Oncology Hematologic||CLL||Syk kinase inhibitor||Spleen tyrosine kinase (Syk)|
Mechanism of action: GS-9973 - An orally available inhibitor of spleen tyrosine kinase (Syk), with potential antineoplastic activity. Upon oral administration of spleen tyrosine kinase inhibitor GS-9973, this agent may inhibit the activity of Syk, which inhibits B-cell receptor (BCR) signaling and leads to an inhibition of tumor cell activation, migration, adhesion and proliferation. Syk, a non-receptor cytoplasmic, BCR-associated tyrosine kinase, is expressed in hematopoietic tissues and is often overexpressed in hematopoeitic malignancies.
Phase of Development: II
Event Type: Data: Phase II trial results
Gilead Announces Updated Phase 2 Results for Investigational GS-9973 in Relapsed Chronic Lymphocytic Leukemia
-- Syk Inhibitor Demonstrates 49 Percent Overall Response Rate with an Estimated Progression-Free Survival Rate at 24 Weeks of 70 Percent in Previously Treated CLL Patients --
-- Data Presented at American Society of Clinical Oncology Annual Meeting --
CHICAGO--(BUSINESS WIRE)--Jun. 3, 2014-- Gilead Sciences, Inc. (NASDAQ: GILD) today announced updated interim results of a Phase 2 study (Study 102) evaluating GS-9973, its investigational oral inhibitor of spleen tyrosine kinase (Syk), for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL). In this study, single-agent treatment with GS-9973 achieved an overall response rate of 49 percent, with an estimated progression-free survival (PFS) rate at 24 weeks of 70 percent. Detailed results will be presented today during an oral session at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstract #7007).
“Most CLL patients eventually relapse following treatment, underscoring the need for novel therapies targeting survival pathways that may enable patients to obtain control of their disease without requiring chemotherapy,” said Jeff Sharman, MD, lead study author and Medical Director of Hematology Research for the US Oncology Network. “The strong response rates and acceptable safety profile seen in this study suggest that GS-9973 has the potential to provide therapeutic benefit for relapsed CLL patients.”
The efficacy analysis focuses on a cohort of 41 CLL patients with a median exposure of 32 weeks (range 1-53) in Study 102. Among this cohort, the Kaplan-Meier estimated PFS rate at 24 weeks was 70 percent (95 percent CI: 51-83 percent). Median PFS and median duration of response were not reached. At the time of data snapshot, 46 percent of patients (n=19) continued GS-9973 treatment. There was a 49 percent (n=20) overall response rate, of which all were partial responses. Ninety-five percent of evaluable patients (n=37/39) experienced tumor shrinkage, including all 25 patients with a chromosome 17p deletion and/or a mutation in the TP53 gene or other genetic abnormalities that have been linked to poor prognosis. Sixty-two percent of evaluable patients (n=24) achieved at least a 50 percent tumor reduction.
The safety of GS-9973 was also assessed in a larger population of 145 CLL or non-Hodgkin lymphoma (NHL) patients with an overall median exposure of 13 weeks at the time of data snapshot. Non-hematologic Grade ≥3 adverse events included fatigue (6.9 percent); dyspnea (6.2 percent); pneumonia (4.1 percent); nausea (3.4 percent); atrial fibrillation, chest pain, dehydration, febrile neutropenia and hypoxia (2.8 percent each); and back pain, hypotension, pyrexia and sepsis (2.1 percent each). Reversible Grade ≥3 transaminase elevations (a measure of liver function) were reported in 14 percent of patients.
Based on these data, Gilead plans to initiate new CLL study cohorts to include patients who have relapsed following treatment with other inhibitors of the b-cell receptor (BCR) pathway.
- See more at: http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=...
Source: press release, 6/03/14. http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=...
1634 Phase 2 Trial Of GS-9973, a Selective Syk Inhibitor, In Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin Lymphoma (NHL)
Program: Oral and Poster Abstracts
Session: 642. CLL: Therapy, excluding Transplantation: Poster I
Saturday, December 7, 2013, 5:30 PM-7:30 PM
Hall E (Ernest N. Morial Convention Center)
Jeff P. Sharman, MD1, Leonard Klein, MD2, Michael Boxer, MD3, Kathryn S. Kolibaba, MD4, Michael J. Hawkins, MD5, Julie A Di Paolo, PhD6*, Jing Hu, Ph.D.7*, Anita Reddy, PhD5*, Feng Jin, PhD5*, Flordeliza Melchor-Khan, BS8* and Christopher A. Yasenchak, MD9
1Willamette Valley Cancer Institute and Research Center/US Oncology Research, Eugene, OR
2Illinois Cancer Specialists, Niles, IL
3Arizona Oncology Associates, Tucson, AZ
4Northwest Cancer Specialists, Vancouver, WA
5Gilead Sciences, Foster City, CA
6Gilead Sciences, Branford, CT
7Oncology, Gilead Sciences, Foster City, CA
8Gilead Sciences, Inc., Foster City, CA
9Northwest Cancer Specialists P.C. US Oncology Research, Tualatin, OR
Introduction: Spleen tyrosine kinase (Syk) is an essential mediator of B-cell receptor signaling in normal and transformed B-cells. GS-9973 is an orally bioavailable, small-molecule, selective inhibitor of Syk. The Kd of GS-9973 for Syk was 7.6 nM with no other kinase < 100 nM (Ambit scanMax at 10 mM).
Methods and Subjects: This Phase 2 trial enrolled subjects with CLL (1 cohort) or NHL (4 cohorts) of 40 subjects each. All subjects were treated with GS-9973 800 mg BID. Tumor imaging was conducted at weeks 8, 16, 24 and every 12 weeks thereafter. Response was evaluated according to standard criteria for CLL (Hallek 2008 and Cheson 2012). GS-9973 plasma levels were obtained throughout the study and concurrently obtained circulating CD5+CD19+ leukemic cells were assessed for changes in pSyk, pBLNK, pBTK and pAKT expression using a PhosFlow protocol. Chemokine/cytokine plasma levels were assessed using multiplexed bead suspension arrays.
Results: This study initiated in March 2013. At time of data lock, 56 subjects with CLL/SLL (32) or NHL(24) have been enrolled. 18 subjects with CLL/SLL and 16 subjects with NHL (10 iNHL, 3 DLBCL and 3 MCL) have completed ≥ 4 weeks of treatment and are included in the safety analysis. Median age was 71 (range 55 - 88), 65% were male. The median number of prior treatment regimens was 5 (range 1-14). All CLL/SLL subjects had received an anti-CD20 antibody, 89% had received an alkylating agent (56% had bendamustine) and 72% had received fludarabine.
Investigator assessed week 8 efficacy analysis is available for 22/54 patients which included 13 CLL/SLL subjects, 7 of whom had 17p deletions and/or TP53 mutations. At the week 8 evaluation all subjects experienced reduced tumor bulk: 4 subjects achieved a decrease of > 50% in their measurable lymph node disease; 8 had < 50% decrease. One subject with a marked decrease in peripheral lymphadenopathy had unequivocal progression of non-measurable mediastinal disease and was considered to have disease progression. The waterfall plot is provided; the striped bars represent those CLL/SLL subjects with a 17p deletion and/or TP53 mutation.
More results including graphs
Source: ASH Abstracts. https://ash.confex.com/ash/2013/webprogram/Paper56543.html