Ibrutinib Three Year Follow-up of Single-Agent and Combination Study Results in Chronic Lymphocytic Leukemia (1)

BEERSE, Belgium, May 31, 2014 /PRNewswire/ --

/NOT INTENDED FOR UK MEDIA/

Oral presentation (Abstract 7014) and poster session (Abstract 7009)

featured at the 50th annual meeting of the American Society of Clinical Oncology

Three year follow-up data from the Phase 1b/2 PCYC-1102 trial of monotherapy ibrutinib showed continued durable responses in patients with treatment-naïve (TN) or relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to data from an analysis that will be discussed in an oral presentation on Tuesday, June 3 at the American Society of Clinical Oncology (ASCO) 50th annual meeting in Chicago, IL. Ibrutinib is an investigational compound in the EU within a class of medicines called Bruton's tyrosine kinase (BTK) inhibitors*.

Janssen announced the results today, which show ibrutinib monotherapy continued to produce high overall response rates (ORR) (78 percent for all treated patients, with the median duration of response not achieved after almost 30 months and 25 months for patients with del 17p). Moreover, the rate of Grade 3 or higher adverse events (AEs) and serious adverse events or those leading to hospitalisation decreased after one year on treatment.

In a separate poster presentation to be discussed today, data suggest the combination of single-agent ibrutinib administered orally once-daily with ofatumumab, a CD20-directed cytolytic monoclonal antibody administered intravenously, is tolerable in patients with previously treated relapsed or refractory CLL/SLL.

In 2011, Janssen and Pharmacyclics Inc. entered into an agreement to jointly develop and commercialise ibrutinib.

Three Year Follow-up of Single Agent Ibrutinib in Phase 1b/2 Trial

Three year follow-up from the initial Phase 1b/2 PCYC-1102 trial of single-agent ibrutinib showed continued durable responses in patients with treatment-naïve (TN) (n=31) or relapsed or refractory CLL or SLL (n=101). Ibrutinib was associated with a 78 percent ORR, with durable responses regardless of prior treatment history (83.9 percent in treatment-naïve patients, 76.2 percent in relapsed or refractory patients, 55.9 percent in relapsed or refractory patients with a deletion of the short arm of chromosome 17 [del 17p]). In addition, five patients with relapsed or refractory CLL and two with del 17p achieved a partial response (PR) with lymphocytosis as best response. Patients received either single-agent ibrutinib once-daily at either 420 mg or 840 mg daily. ORR was assessed based on International Working Committee on Chronic Lymphocytic Leukemia (IWCLL) criteria. The median time on study was 29.4 months (range, 0.7-38.1 months).

The median duration of response was not achieved for the full set of patients (n=132) evaluated for the analysis. For relapsed or refractory patients with del 17p, the median duration of response was 25 months (range 4.8-34.3 months).

"These results suggest significantly extended response to ibrutinib in patients with CLL three years after starting treatment," said Professor Ulrich Jäger, Medical University of Vienna, Department of Medicine, Division of Haematology and Hemostaseology. "We are especially encouraged to see that patients showed durable responses to treatment with ibrutinib monotherapy regardless of their treatment history."

Grade 3 or 4 AEs in the pooled analysis related to ibrutinib (investigator-assessed) decreased from 24 percent to four percent after three years of follow-up. Grade 3 or higher serious AEs (SAEs) related to ibrutinib also decreased over time from eight percent in the first year to one percent after three years of treatment. No new safety signals were observed in long-term follow-up and 64 percent of patients remain on treatment with ibrutinib. The rate of Grade 3 or higher adverse events or those leading to hospitalisation decreased after one year on treatment with ibrutinib.

Combination Data

Separately, data from the Phase 1b/2 PCYC-1109 study, to be presented today at ASCO, showed treatment with monotherapy ibrutinib administered once-daily in combination with ofatumumab administered intravenously is tolerated and highly active in patients with relapsed or refractory CLL/SLL (n=71). The combination produced an 83 percent ORR in patients across all three dosing regimens studied, including a 100 percent ORR (n=27) in patients who started with one cycle of ibrutinib therapy followed by ofatumumab; additionally, two patients in the study achieved a PR with lymphocytosis. Additionally, at 12 months, the average progression-free survival (PFS) across all patients was approximately 88 percent, with 64 percent of patients continuing on monotherapy ibrutinib in a long-term extension study. Three patients with Richter's transformation receiving ibrutinib and ofatumumab achieved disease control followed by progression after Day 471, 168 and 137, respectively.

        
                                                  Group 2: ofatumumab   Group 3: two cycles of
                          Group 1: one cycle     on day one/cycle one   ofatumumab monotherapy,    
             N=71        ibrutinib monotherapy,    and ibrutinib on      followed by ibrutinib
                        followed by ofatumumab     day two/cycle one    on day one/cycle three
                                (n=27)                  (n=20)                  (n=24)

        ORR                      100%                     79%                     71%
        PFS at 12 months          89%                     85%                     90%
        Median duration
        of response           Not reached             Not reached             Not reached
        Best response         100% (n=23)              84% (n=19)              75% (n=24)

The most common Grade 3 or 4 AE in the study (occurring in 10 percent or more of patients) was neutropenia (17%). The most frequent AEs (occurring in 20% or more of patients) were diarrhoea (68%), infusion-related reaction (45%), peripheral sensory neuropathy (nerve damage; 42%) and stomatitis (inflammation of the mouth and lips; 37%). Six patients (8%) experienced AEs leading to discontinuation of treatment with ibrutinib. Nine patients (12.7%) died within 30 days of the last dose and two died within the follow-up period.

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