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Open‐label, single‐arm, phase II study of enzastaurin in patients with follicular lymphoma
Author(s) -
Schwartzberg Lee,
Hermann Robert,
Flinn Ian,
Flora Douglas,
Hsi Eric D.,
Hamid Oday,
Shi Peipei,
Lin Boris K.,
Myrand Scott P.,
Nguyen Tuan S.,
Dreyling Martin
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12853
Subject(s) - medicine , nausea , follicular lymphoma , adverse effect , phases of clinical research , clinical endpoint , toxicity , gastroenterology , lymphoma , loading dose , oncology , pharmacology , clinical trial
Summary This open‐label, phase II study investigated whether enzastaurin, a protein kinase C‐beta ( PKC β) inhibitor, had activity in patients with grade 1 or 2 follicular lymphoma ( FL ). Adults with grade 1 or 2 FL who had no more than one prior treatment received oral enzastaurin continuously for up to 3 years. Of the 66 patients who received enzastaurin, 53 were evaluable for response. Overall response rate ( ORR , primary efficacy endpoint) was 26·4% (3·8% complete response). Median (95% confidence interval) progression‐free survival, time to response, and duration of response were 18·1 (11·5–28·3), 4·9 (2·8–8·1), and 22·3 (8·8‐not applicable) months, respectively. In patients with tumour tissue available for biomarker analysis, ORR s in low versus high PKC β2 expression groups were 41·7% and 8·3%, respectively ( P = 0·041). The most common, mainly low‐grade drug‐related adverse events were fatigue (25·8%), diarrhoea (25·8%), nausea (18·2%), and chromaturia (18·2%). Four (6·1%) patients had Grade 3 toxicity and one (1·5%) patient had Grade 4 toxicity. Enzastaurin demonstrated limited clinical activity in grade 1 or 2 FL . Patients with low PKC β2 expression in tumours had higher ORR than those with high PKC β2 expression. Enzastaurin was well tolerated with mostly grade 1 or 2 toxicities. Further studies may be warranted in select patient populations.