Updated interim results of a phase 2 study ( Study 102 ) evaluating GS-9973, an investigational oral inhibitor of spleen tyrosine kinase ( Syk ), for the treatment of patients with relapsed chronic lymphocytic leukemia ( CLL ) were presented.
In this study, single-agent treatment with GS-9973 has achieved an overall response rate of 49%, with an estimated progression-free survival rate at 24 weeks of 70%.
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 progression-free survival rate at 24 weeks was 70%.
Median progression-free survival and median duration of response were not reached.
At the time of data snapshot, 46% of patients ( n=19 ) continued GS-9973 treatment.
There was a 49% ( n=20 ) overall response rate, of which all were partial responses. Ninety-five percent of evaluable patients ( n=37/39 ) has 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% 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 greater than or equal to 3 adverse events included fatigue ( 6.9% ); dyspnea ( 6.2% ); pneumonia ( 4.1% ); nausea ( 3.4% ); atrial fibrillation, chest pain, dehydration, febrile neutropenia and hypoxia ( 2.8% each ); and back pain, hypotension, pyrexia and sepsis ( 2.1% each ).
Reversible Grade greater than or equal to 3 transaminase elevations ( a measure of liver function ) were reported in 14% of patients.
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 and NHL ( indolent NHL, diffuse large B-cell lymphoma and mantle cell lymphoma ).
The median age of the CLL patients included in the analysis was 73 years. These patients had received a median of two prior treatment regimens ( e.g., anti-CD20 antibodies, alkylating agents, Fludarabine ) before study entry ( range: 1-8 ).
The primary endpoint of the study is progression-free survival at week 24 for the CLL cohort.
Patients are allowed to continue daily dosing as long as they benefit from therapy.
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.
Chronic lymphocytic leukemia is a slow-growing cancer in which the bone marrow overproduces white blood cells, leaving less room in the bone marrow and blood 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 anemia and serious infections.
The National Cancer Institute ( NCI ) estimates that in 2013, there were approximately 16,000 new CLL diagnoses in the United States and 4,500 deaths related to this cancer. ( Xagena )
Source: 50th Annual Meeting of the American Society of Clinical Oncology ( ASCO ), 2014