Gilead Sciences, Inc., a biopharmaceutical company, 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 leukaemia (CLL). In Study 119, there was a 73 per cent 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 per cent CI: 0.19, 0.39; p<0.0001). Detailed results presented during a poster session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstract #7023).
"The data reported reinforce prior results showing that idelalisib, here in combination with the anti-CD20 monoclonal antibody ofatumumab, not only significantly improved overall and lymph node response rates, but more importantly progression-free survival in patients with previously treated CLL," said Jeffrey A. Jones, MD, MPH, Associate Professor of Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James). "Importantly, these improvements were also observed in patients with genetic features typically associated with poor prognosis."
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).
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 per cent vs. 4.9 per cent; OR=486.96, p<0.0001). Median PFS in the approximately 40 per cent 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 diarrhoea/colitis (20.2 percent), pneumonia (12.7 per cent) and febrile neutropenia (11.6 per cent).
Based on the Study 119 trial results, Gilead has filed a supplemental New Drug Application (sNDA) with the US Food and Drug Administration to include data from this study in the US label. Gilead plans to submit a supplemental filing to the European Medicines Agency later this year.
"Zydelig has now demonstrated strong efficacy in two randomized phase 3 studies among previously treated CLL patients," said Norbert Bischofberger, PhD, Gilead's executive vice president, research and development and chief scientific officer. "We continue to explore the clinical profile of Zydelig in combination with both standard and novel treatment regimens, including seven ongoing or completed Phase 3 clinical trials for B-cell malignancies."
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need.