PURPOSE: @entity17528 is a @entity16629 inhibitor with significant preclinical activity in @entity1582 ( @entity1582 ) cells. This phase 2 study used a two-stage Simon design to determine the @entity17528 response rate in @entity1 with relapsed or refractory @entity1582 . EXPERIMENTAL DESIGN: @entity17528 (75 mg) was administered orally, twice a day, continuously for 28-day cycles. Response was evaluated after 3 cycles. RESULTS: Thirty-six @entity1 received therapy. The median age was 65 years (range: 43-81) and the median number of prior therapies was 5 (range: 2-11). The most common grade 3 and 4 @entity137 included @entity417 , @entity1398 , @entity882 , @entity294 , and @entity1295 . Three @entity204 occurred possibly related to @entity17528 (2 due to @entity295 , 1 due to @entity810 ). After @entity17528 discontinuation, 3 additional @entity204 occurred due to disease progression. The response rate (CR + PR) was 5.6% with a mean duration of response of 4.95 months and median progression-free survival time of 3.52 months. One @entity1 had a very good partial response (VGPR), 1 @entity1 had a partial response, 17 @entity1 had stable disease, 13 @entity1 had @entity74 @entity1 could not be assessed for response. Pharmacodynamic studies revealed variable effects on bone marrow CD138+ cell @entity16629 and @entity1366 phosphorylation. The best clinical response, a prolonged VGPR, occurred in a @entity1 with an @entity50601 translocation. CONCLUSIONS: Single-agent @entity17528 was tolerable and had minimal activity in this heavily pre-treated population.

A Phase 2 Trial of @entity17528 ( @entity17528 , @entity17528 ), an Oral @entity16629 Inhibitor, in Relapsed/Refractory XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicities'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity417 :: ('MESH:D000740', 'Disease') :: ['anemia'] @entity882 :: ('MESH:D013921', 'Disease') :: ['thrombocytopenia'] @entity294 :: ('MESH:D003967', 'Disease') :: ['diarrhea'] @entity1295 :: ('MESH:D005221', 'Disease') :: ['fatigue'] @entity16629 :: ('5604;5605', 'Gene') :: ['MEK1/2'] @entity1582 :: ('MESH:D009101', 'Disease') :: ['multiple myeloma', 'MM'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia'] @entity74 :: ('MESH:D030342', 'Disease') :: ['progressive disease, and 4'] @entity810 :: ('MESH:D058186', 'Disease') :: ['acute kidney injury'] @entity17528 :: ('MESH:C517975', 'Chemical') :: ['AZD6244'] @entity204 :: ('MESH:D003643', 'Disease') :: ['deaths'] @entity50601 :: ('7468', 'Gene') :: ['MMSET'] @entity1366 :: ('5595;5594', 'Gene') :: ['ERK1/2']
@entity1582 :: (MESH:D009101,Disease) :: ['Multiple Myeloma']
