First-in-human phase 1 study of the BTK inhibitor GDC-0853 in relapsed or refractory B-cell NHL and CLL

John C. Byrd, Stephen Smith, Nina Wagner-Johnston, Jeff Sharman, Andy I. Chen, Ranjana Advani, Bradley Augustson, Paula Marlton, S. Renee Commerford, Kwame Okrah, Lichuan Liu, Elaine Murray, Elicia Penuel, Ashley F. Ward, Ian W. Flinn

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


GDC-0853 is a selective, reversible, and non-covalent inhibitor of Bruton's tyrosine kinase (BTK) that does not require interaction with the Cys481 residue for activity. In this first-in-human phase 1 study we evaluated safety, tolerability, pharmacokinetics, and activity of GDC-0853 in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Twenty-four patients, enrolled into 3 cohorts, including 6 patients who were positive for the C481S mutation, received GDC-0853 at 100, 200, or 400 mg once daily, orally. There were no dose limiting toxicities. GDC-0853 was well tolerated and the maximum tolerated dose (MTD) was not reached due to premature study closure. Common adverse events (AEs) in ≥ 15% of patients regardless of causality included fatigue (37%), nausea (33%), diarrhea (29%), thrombocytopenia (25%), headache (20%), and abdominal pain, cough, and dizziness (16%, each). Nine serious AEs were reported in 5 patients of whom 2 had fatal outcomes (confirmed H1N1 influenza and influenza pneumonia). A third death was due to progressive disease. Eight of 24 patients responded to GDC-0853: 1 complete response, 4 partial responses, and 3 partial responses with lymphocytosis, including 1 patient with the C481S mutation. Two additional C481S mutation patients had a decrease in size of target tumors (-23% and -44%). These data demonstrate GDC-0853 was generally well-tolerated with antitumor activity.

Original languageEnglish (US)
Pages (from-to)13023-13035
Number of pages13
Issue number16
StatePublished - 2018


  • BTK
  • CLL
  • GCD0853

ASJC Scopus subject areas

  • Oncology


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