Ibrutinib Improved Survival For Treatment-Naive CLL Patients In RESONATE-2 Trial

(RTTNews) - Pharmacyclics LLC, an AbbVie (ABBV) company, announced that ibrutinib or IMBRUVICA improved progression-free survival (PFS; primary endpoint) and multiple secondary endpoints including overall survival or OS and overall response rate (ORR) in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL, respectively) in the final analysis of the Phase III RESONATE-2 (PCYC-1115) trial.

RESONATE-2 is a randomized, multi-center, open-label study assessing the use of ibrutinib versus chlorambucil in treatment-naïve CLL/SLL patients aged 65 years or older.

This is the first head-to-head trial in the clinical program that evaluates the safety and efficacy of ibrutinib versus traditional chemotherapy. IMBRUVICA is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

RESONATE-2 is a Pharmacyclics-sponsored trial and its protocol and specific performance goals were established in a special protocol assessment or SPA with the U.S. Food and Drug Administration.

A SPA is an agreement with the FDA that an ongoing Phase III clinical trial design, its clinical endpoints, and other statistical analyses are acceptable to the Agency to support an approval. The trial enrolled 269 patients with CLL/SLL aged 65 years or older without prior treatment in the U.S., EU and other regions.

CLL patients with deletion of the short arm of chromosome 17 (del 17p CLL) were excluded from the trial since single-agent chlorambucil is not an effective therapy in this population. Patients were randomized to receive either ibrutinib 420 mg orally, once daily until progression or toxicity or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in Cycle 1 was 0.5 mg/kg and was increased based on tolerability in Cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.

The primary endpoint of the study was PFS as assessed by an Independent Review Committee according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis. Key secondary endpoints included ORR, OS, and safety.