Date: 2015-08-27
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Gilead (USA - CA)
Product: Zydelig® (idelalisib) and ofatumumab
Action
mechanism: kinase inhibitor/phosphoinositide 3-kinase (PI3K) inhibitor/monoclonal antibody. Zydelig® is an oral inhibitor of phosphoinositide 3-kinase (PI3K) delta, a protein that plays a role in the activation, proliferation and viability of B cells. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and by inhibiting the protein, Zydelig blocks several cellular signaling pathways that drive B-cell viability. Ofatumumab is a human monoclonal antibody which targets an epitope on the CD20 molecule encompassing parts of the small and large extracellular loops. The drug has been developed under a co-development and commercialization agreement between Genmab and GSK. In April 2014, Novartis has agreed to acquire GSK oncology products including ofatumumab.
Disease: previously-treated patients with chronic lymphocytic leukemia (CLL)
Therapeutic area: Cancer - Oncology
Country:
Trial
details: Study 119 was a randomized, controlled, open-label Phase 3 study evaluating the efficacy and safety of Zydelig in combination with ofatumumab. The study enrolled 261 adult patients with previously treated CLL whose disease had progressed less than 24 months following completion of prior therapy, and had not previously been refractory to ofatumumab. Eligible patients were randomized 2:1 to receive an ofatumumab 1,000 mg dosing regimen (12 infusions, first infusion 300mg) over 24 weeks plus Zydelig (150 mg) twice daily (n=174) continuously until disease progression or unacceptable toxicity or an ofatumumab 2,000 mg dosing regimen (12 infusions, first infusion 300mg) over 24 weeks (n=87).
Latest
news: * On May 31, 2015, Gilead Sciences announced results from the Phase 3 clinical Study 119 of an investigational use of Zydelig® (idelalisib) in combination with ofatumumab in previously-treated patients with chronic lymphocytic leukemia (CLL). In Study 119, there was a 73 percent reduction in the risk of disease progression or death in patients receiving Zydelig® in combination with ofatumumab compared to ofatumumab alone (hazard ratio (HR) = 0.27; 95 percent CI: 0.19, 0.39; p<0.0001). Detailed results will be presented during a poster session at the 51st Annual Meeting of the American Society of Clinical Oncology ( ASCO ) in Chicago (Abstract #7023). The study enrolled 261 adult patients with previously treated CLL whose disease had progressed less than 24 months following completion of prior therapy, and had not previously been refractory to ofatumumab. Eligible patients were randomized 2:1 to receive an ofatumumab 1,000 mg dosing regimen (12 infusions, first infusion 300mg) over 24 weeks plus Zydelig® (150 mg) twice daily (n=174) continuously until disease progression or unacceptable toxicity or an ofatumumab 2,000 mg dosing regimen (12 infusions, first infusion 300mg) over 24 weeks (n=87). The primary endpoint was progression-free survival (PFS), defined as the time from randomization to definitive disease progression or death assessed by an independent review committee. Median PFS in the Zydelig®/ofatumumab arm was 16.3 months, compared to 8.0 months in the ofatumumab monotherapy arm. Statistically significant improvements were also observed for overall response rate (75 percent vs. 18 percent; odds ratio (OR) = 15.9, p<0.0001) and lymph node response rate (93.3 percent vs. 4.9 percent; OR=486.96, p<0.0001). Median PFS in the approximately 40 percent of patients with 17p deletion or TP53 mutation was 13.7 months vs. 5.8 months (HR=0.32, p<0.0001). A statistically significant difference was not achieved in median overall survival (20.9 months vs. 19.4 months; HR=0.74, p=0.27). The safety profile of Zydelig® was similar to prior studies in previously-treated patients with CLL. Grade =3 adverse events occurring in the Zydelig® plus ofatumumab arm included diarrhea/colitis (20.2 percent), pneumonia (12.7 percent) and febrile neutropenia (11.6 percent). Based on the Study 119 trial results, Gilead has filed a supplemental New Drug Application (sNDA) with the FDA to include data from this study in the U.S. label. Gilead plans to submit a supplemental filing to the European Medicines Agency later this year.
