Pharmacyclics's Phase III RESONATE™ trial shows adherence to 420mg dose of IMBRUVICA improves outcomes in CLL patients

Pharmacyclics LLC today highlighted results from a sub-analysis of the Phase III RESONATE^™ (PCYC-1112) trial, which found that previously-treated patients with chronic lymphocytic leukemia (CLL) who adhered to the recommended 420 mg dose of IMBRUVICA^® (ibrutinib) experienced improved progression-free survival (PFS; the primary endpoint) as assessed by an Independent Review Committee (IRC), compared to patients who took lower doses or missed doses, regardless of high-risk genetic factors. The data will be presented today at the 51^st American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL at 8:00 a.m. CT. IMBRUVICA is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

"These data show that when patients take IMBRUVICA daily, at the recommended dose, it can improve their chance of achieving a sustained treatment response and delay disease progression," said Paul Barr, M.D., Assistant Professor of Medicine and Director of the Clinical Trials Office, Wilmot Cancer Institute, Rochester, NY and lead presenter of the sub-analysis data. "As clinicians, it is important that we ensure that patients take this once-daily, oral medication as recommended in order to achieve the best possible outcome in treating their cancer."

The poster provides insights from the RESONATE trial specific to the importance of adhering to the recommended 420 mg once-daily dose of IMBRUVICA in previously-treated CLL patients (n=195). After 8.3 months of treatment, patients treated with IMBRUVICA had a mean dose intensity – defined as the proportion of actually administered versus planned doses of IMBRUVICA 420 mg – of 95% (median 100%). The majority of dose interruptions restarted at 420 mg; 3.6% of patients experienced one dose reduction and 0.5% experienced two dose reductions due to adverse events (AEs).

Notably, the recommended 420 mg dose was associated with longer PFS rates (median not reached) compared to those patients who took lower doses (11 months), regardless of high-risk factors including del 17p, del 11q or p53 mutations. Patients who consistently missed their IMBRUVICA dose for eight or more consecutive days experienced more events compared to patients who did not experience such dose holds (31% vs. 13%, respectively). The mean duration of missed doses in patients who missed more than one week of therapy was 26 days.

"This sub-analysis confirms the strength of IMBRUVICA's clinical benefit when the recommended dose is taken correctly and consistently," said Elizabeth Faust, Ph.D., Head of Medical Affairs at Pharmacyclics. "We are encouraged to see many of the patients in the RESONATE trial who take the therapy as directed continue to do well, demonstrating the importance of using IMBRUVICA at the recommended daily dose to achieve the best possible response."

The most frequent (>20%) non-hematologic AEs seen in the broader RESONATE trial were diarrhea, fatigue, pyrexia and nausea in the IMBRUVICA-treated group and fatigue, infusion-related reactions and cough in the ofatumumab-treated group. Treatment exposure was longer among patients receiving ibrutinib vs. ofatumumab (median duration, 8.6 vs. 5.3 months).

RESONATE is a randomized, multi-center, international, head-to-head comparison of single-agent, orally-administered IMBRUVICA versus the intravenous, monoclonal antibody ofatumumab targeting the CD20 antigen. This study enrolled 373 patients with CLL and 18 patients with small lymphocytic lymphoma (SLL), who had received at least one prior therapy. The median number of prior treatments was two (range, 1 to 13 treatments). At baseline, the median age of these patients was 67 years, 58% of whom had at least one tumor larger than 5 cm, and 32% of whom had the del 17p mutation. In the trial, patients receiving IMBRUVICA demonstrated a statistically significant improvement in PFS, overall survival (OS) and overall response rate (ORR) as compared to patients treated with ofatumumab.