IDMC recommends early stopping of Phase 3 study of ibrutinib in treatment of CLL/SLL

Janssen-Cilag International NV (Janssen) today announced the early stopping of PCYC-1112-CA, the Phase 3 study of ibrutinib in the treatment of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL), based on the recommendation of an Independent Data Monitoring Committee (IDMC), which concluded that the study showed a significant difference in progression-free survival (PFS) as compared to the control, the primary endpoint of the study.

Study PCYC-1112-CA (RESONATE) is an international, randomized, open-label Phase 3 clinical study including 391 patients with relapsed or refractory CLL/SLL with measurable nodal disease and who were not eligible for treatment with purine analog-based therapy, who had received at least one prior therapy. Patients were randomized to receive 420 mg of ibrutinib orally once daily or intravenous doses of ofatumumab, an approved treatment for relapsed/refractory CLL, over the course of 24 weeks. Both treatments were administered until disease progression or unacceptable toxicity.

The primary endpoint of the study is PFS; overall survival (OS) is a key secondary endpoint; others included overall response rate and safety.

"We're delighted with this outcome, and look forward to sharing these results with the scientific community and Health Authorities," said Peter F. Lebowitz, MD, PhD, Oncology Therapeutic Area Head, Janssen Research & Development, LLC. "This Phase 3 randomized study provides a useful head-to-head comparison of single agent ibrutinib versus ofatumumab, and builds upon the early evidence of clinical benefit observed in the ibrutinib Phase 2 programme."

The IDMC unanimously recommended stopping of the study early based on a planned interim analysis, in which statistically significant differences in PFS (as assessed by an independent review committee) and OS were observed. The IDMC agreed that these results suggest evidence of clinical benefit as well as a tolerable safety profile in patients receiving ibrutinib as compared to intravenous doses of ofatumumab. The IDMC also recommended that the sponsor provides access to ibrutinib to patients in the ofatumumab arm.

These results will be presented at an upcoming medical meeting and also will be submitted for publication in a peer-reviewed journal.

The company plans to initiate a Named Patient Programme for high risk patients with relapsed or refractory CLL/SLL or relapsed or refractory MCL (Mantle Cell Lymphoma) in Europe in the first half of 2014.

On October 30, 2013, Janssen submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for ibrutinib for the treatment of adult patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) or relapsed or refractory Mantle Cell Lymphoma (MCL).

CLL/SLL and MCL belong to a group of blood cancers, known as B-cell malignancies, originating from B cells, a type of white blood cell (lymphocyte).¹ CLL/SLL and MCL are complex diseases that can be challenging to treat. As a result, many patients will relapse after a specific treatment and may require multiple treatments over the course of their disease.