Janssen Research & Development, LLC (Janssen) announced that the phase 3 iNNOVATE (PCYC-1127) study evaluating Imbruvica (ibrutinib) in combination with rituximab (Rituxan) in relapsed/refractory and treatment-naïve patients with Waldenström’s macroglobulinemia (WM) successfully met its primary endpoint of progression-free survival (PFS).

An Independent Data Monitoring Committee (IDMC) recommended unblinding iNNOVATE based on efficacy results observed in the pre-specified interim analysis. Imbruvica is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor jointly developed and commercialized by Janssen Biotech and Pharmacyclics LLC, an AbbVie company.

“It is gratifying to see that patients with Waldenström’s macroglobulinemia – a rare, difficult-to-treat form of blood cancer – have achieved this magnitude of benefit with the Imbruvica combination with rituximab as compared to rituximab alone in either the relapsed/refractory or newly diagnosed setting,” said Craig Tendler, M.D., vice president, Late-Stage Development and Global Medical Affairs, Janssen Oncology. “Since the approval of Imbruvica in 2013 for Waldenström’s, we have added to the body of evidence and patient experience, by conducting this randomized Phase 3 trial and confirming Imbruvica’s clinical benefit first seen in the relapsed/refractory setting and now demonstrated with earlier use in the treatment journey for the WM patient.”
 
Janssen and Pharmacyclics will share and discuss the unblinded data from the study with health authorities around the world. Imbruvica received FDA approval in WM in January 2015.

iNNOVATE is a Pharmacyclics-sponsored, randomized, placebo-controlled, double-blind, phase 3 study, which is evaluating Imbruvica (ibrutinib) in combination with rituximab, and placebo in combination with rituximab in 150 patients with relapsed/refractory and treatment-naïve Waldenström’s macroglobulinemia (WM). In the study, patients were randomized to receive intravenous rituximab 375 mg/m 2 once weekly for four consecutive weeks, followed by a second four-weekly rituximab course following a three-month interval. All patients received either Imbruvica420 mg or placebo once daily continuously until criteria for permanent discontinuation were met. The primary endpoint is progression-free survival, with secondary objectives including overall response rate, hematological improvement measured by hemoglobin, time-to-next treatment, overall survival, and number of participants with adverse events as a measure of safety and tolerability within each treatment arm. WM is a form of non-Hodgkin’s lymphoma and is a rare disease, with an incidence rate of about three cases per million per year in the US. Roughly 1,000 to 1,500 people are diagnosed with WM each year in the US.

Imbruvica (ibrutinib) was one of the first therapies to receive US approval after having received the FDA’s Breakthrough Therapy Designation. Imbruvica works by blocking a specific protein called Bruton's tyrosine kinase (BTK). The BTK protein transmits important signals that tell B cells to mature and produce antibodies and is needed by specific cancer cells to multiply and spread.\3 Imbruvica targets and blocks BTK, inhibiting the survival and spread of cancer cells, and impacting signaling associated with other serious conditions. Worldwide, Imbruvica was used to treat more than 90,000 patients to date.