Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (32156743)
Authors Danilov AV, Herbaux C, Walter HS, Hillmen P, Rule SA, Kio EA, Karlin L, Dyer MJS, Mitra SS, Yi PC, Humeniuk R, Huang X, Zhou Z, Bhargava P, Jürgensmeier JM, Fegan CD
Title Phase Ib Study of Tirabrutinib in Combination with Idelalisib or Entospletinib in Previously Treated Chronic Lymphocytic Leukemia.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 26
Issue 12
Date 2020 Jun 15
URL
Abstract Text Bruton tyrosine kinase (BTK) inhibition alone leads to incomplete responses in chronic lymphocytic leukemia (CLL). Combination therapy may reduce activation of escape pathways and deepen responses. This open-label, phase Ib, sequential dose-escalation and dose-expansion study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of the selective BTK inhibitor tirabrutinib alone, in combination with the PI3K delta (PI3Kδ) inhibitor idelalisib, or with the spleen tyrosine kinase (SYK) inhibitor entospletinib in patients with relapsed/refractory CLL.Patients received either tirabrutinib monotherapy (80 mg every day) or tirabrutinib 20-150 mg every day in combination with either idelalisib (50 mg twice a day or 100 mg every day) or entospletinib (200 mg or 400 mg every day).Fifty-three patients were included. Systemic tirabrutinib exposure was comparable between monotherapy and combination therapy. No MTD was identified. Across all treatment groups, the most common adverse event was diarrhea (43%, 1 patient grade ≥3); discontinuation due to adverse events was uncommon (13%). Objective response rates were 83%, 93%, and 100%, and complete responses were 7%, 7%, and 10% in patients receiving tirabrutinib, tirabrutinib/idelalisib, and tirabrutinib/entospletinib, respectively. As of February 21, 2019, 46 of 53 patients continue to receive treatment on study.Tirabrutinib in combination with idelalisib or entospletinib was well tolerated in patients with CLL, establishing an acceptable safety profile for concurrent selective inhibition of BTK with either PI3Kδ or SYK. This small study did not establish a superior efficacy of the combinations over tirabrutinib alone. This trial is registered at www.clinicaltrials.gov (NCT02457598).

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Entospletinib GS-9973|GS 9973|GS9973 SYK Inhibitor 13 Entospletinib (GS-9973) is a selective spleen tyrosine kinase (Syk) inhibitor, which in turn inhibits B-cell receptor signaling, leading to suppression of cell migration and inhibition of survival (PMID: 24779514, PMID: 32156743).
Tirabrutinib ONO-GS-4059|ONO-WG-307|ONO-4059 BTK inhibitor 22 Tirabrutinib (ONO-4059) inhibits Bruton's Tyrosine Kinase (BTK), which leads to decreased B-cell proliferation and differentiation, and may have antitumor activity in B-cell malignancies (PMID: 23958373, PMID: 27776353, PMID: 32156743).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown chronic lymphocytic leukemia not applicable Tirabrutinib Phase I Actionable In a Phase Ib trial, Tirabrutinib (ONO-4059) treatment was well tolerated, resulted in a overall response rate of 83% (24/29) with complete response in 7% (2/29) of patients with chronic lymphocytic leukemia (PMID: 32156743; NCT02457598). 32156743
Unknown unknown chronic lymphocytic leukemia not applicable Idelalisib + Tirabrutinib Phase I Actionable In a Phase Ib trial, Tirabrutinib (ONO-4059) and Zydelig (idelalisib) combination treatment was well tolerated, resulted in a overall response rate of 93% (13/14) with complete response in 7% (1/14) of patients with chronic lymphocytic leukemia (PMID: 32156743; NCT02457598). 32156743
Unknown unknown chronic lymphocytic leukemia not applicable Entospletinib + Tirabrutinib Phase I Actionable In a Phase Ib trial, Tirabrutinib (ONO-4059) and Entospletinib combination treatment was well tolerated, resulted in a overall response rate of 100% (10/10) with complete response in 10% (1/10) of patients with chronic lymphocytic leukemia (PMID: 32156743; NCT02457598). 32156743