Unknown

Dataset Information

0

An Open-label, Phase II Trial of Entospletinib (GS-9973), a Selective Spleen Tyrosine Kinase Inhibitor, in Diffuse Large B-cell Lymphoma.


ABSTRACT: BACKGROUND:Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. Entospletinib monotherapy was evaluated in a multicenter, phase II study of subjects with relapsed or refractory B-cell malignancy. PATIENTS AND METHODS:The study included 43 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The participants received 800 mg of the original, monomesylate formulation of entospletinib twice daily as a starting dose; the doses could be reduced because of toxicity throughout the study. RESULTS:No patient achieved a complete or partial response, 5 patients (12%) had stable disease, and 26 patients (60%) had progressive disease. Progression-free survival (PFS) at 16 weeks was 3.6% (95% confidence interval [CI], 0.3%-15.3%), and the median PFS was 1.5 months (95% CI, 1-1.7 months). The independent review committee-assessed nodal response for 27 evaluable patients showed a reduced tumor burden in 6 patients (22%). The median duration of entospletinib treatment for these 6 patients was 9 weeks (range, 3-24 weeks). One patient (4%) had a decrease of ? 50% in the sum of the product of the nodal diameters. The treatment-emergent adverse events occurring in ? 20% of the cohort were fatigue, nausea, decreased appetite, constipation, dyspnea, diarrhea, dehydration, cough, insomnia, and peripheral edema. The common laboratory abnormalities occurring in ? 20% of the subjects were lymphocytopenia, anemia, creatinine (chronic kidney disease), increased aspartate aminotransferase, hypoalbuminemia, total bilirubin, hyponatremia, leukopenia, increased alanine aminotransferase, increased alkaline phosphatase, and hyperglycemia. CONCLUSION:Entospletinib monotherapy at 800 mg twice daily demonstrated limited activity in patients with advanced, relapsed DLBCL.

SUBMITTER: Burke JM 

PROVIDER: S-EPMC6857170 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

An Open-label, Phase II Trial of Entospletinib (GS-9973), a Selective Spleen Tyrosine Kinase Inhibitor, in Diffuse Large B-cell Lymphoma.

Burke John M JM   Shustov Andrei A   Essell James J   Patel-Donnelly Dipti D   Yang Jay J   Chen Robert R   Ye Wei W   Shi Wen W   Assouline Sarit S   Sharman Jeff J  

Clinical lymphoma, myeloma & leukemia 20180606 8


<h4>Background</h4>Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. Entospletinib monotherapy was evaluated in a multicenter, phase II study of subjects with relapsed or refractory B-cell malignancy.<h4>Patients and methods</h4>The study included 43 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The participants received 800 mg of the original, monomesylate formulation of entospletinib twice daily as a starting dose; the doses could  ...[more]

Similar Datasets

| S-EPMC4401348 | biostudies-literature
| S-EPMC8315011 | biostudies-literature
| S-EPMC6585960 | biostudies-literature
| S-EPMC7153012 | biostudies-literature
| S-EPMC4011593 | biostudies-literature
| S-EPMC8382351 | biostudies-literature
| S-EPMC9644621 | biostudies-literature
| S-EPMC5298344 | biostudies-literature
| S-EPMC5351700 | biostudies-literature
| S-EPMC6106053 | biostudies-literature