@entity6490 in combination with rituximab in relapsed or XXXX : a single-centre, open-label, phase 2 trial.

@entity1 @entity6113 @entity548 @entity326 @entity294 @entity2225 @entity409 @entity4910 @entity1398 @entity1073 @entity955 @entity1167 @entity2408 @entity6490
BACKGROUND: @entity6490 is approved in the EU, USA, and other countries for @entity1 with @entity1073 who received one previous therapy. In a previous phase 2 study with single-agent @entity6490 , the proportion of @entity1 who achieved an objective response was 68%; 38 (34%) of 111 @entity1 had transient @entity6113 . We hypothesised that adding @entity2408 could target @entity1073 cells associated with redistribution @entity6113 , leading to more potent antitumour activity. METHODS: @entity1 with a confirmed @entity1073 diagnosis (based on @entity2225 -positive and @entity4910 -positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. @entity1 received continuous oral @entity6490 (560 mg) daily until progessive disease or unacceptable toxic effects. Rituximab 375 mg/m(2) was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3-8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of @entity1 who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT01880567, and is still ongoing, but no longer accruing @entity1 . FINDINGS: Between July 15, 2013, and June 30, 2014, 50 @entity1 were enrolled. Median age was 67 years (range 45-86), and the median number of previous regimens was three (range 1-9). At a median follow-up of 16  5 months (IQR 12  09-19  28), 44 (88%, 95% CI 75  7-95  5) @entity1 achieved an objective response, with 22 (44%, 30  0-58  7) @entity1 achieving a complete response, and 22 (44%, 30  0-58  7) a partial response. The only grade 3 adverse event in >=10% of @entity1 was @entity955 , which was noted in six (12%) @entity1 . Grade 4 @entity294 and @entity1398 occurred in one @entity1 each. Adverse events led to discontinuation of therapy in five (10%) @entity1 ( @entity955 in three [6%] @entity1 , @entity409 in one [2%], and @entity548 in one [2%]). Two @entity1 died while on-study from @entity1167 and @entity326 ; the latter was deemed possibly related to treatment. INTERPRETATION: @entity6490 combined with rituximab is active and well tolerated in @entity1 with relapsed or @entity1073 . Our results provide preliminary evidence for the activity of this combination in clinical practice. A phase 3 trial is warranted for more definitive data. FUNDING: Pharmacyclics LLC, an AbbVie Company.
