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 (29765150)
Authors Cortes J, Tamura K, DeAngelo DJ, de Bono J, Lorente D, Minden M, Uy GL, Kantarjian H, Chen LS, Gandhi V, Godin R, Keating K, McEachern K, Vishwanathan K, Pease JE, Dean E
Title Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers.
Journal British journal of cancer
Vol 118
Issue 11
Date 2018 05
URL
Abstract Text Proviral integration Moloney virus (PIM) kinases (PIM1, 2 and 3) are overexpressed in several tumour types and contribute to oncogenesis. AZD1208 is a potent ATP-competitive PIM kinase inhibitor investigated in patients with recurrent or refractory acute myeloid leukaemia (AML) or advanced solid tumours.Two dose-escalation studies were performed to evaluate the safety and tolerability, and to define the maximum tolerated dose (MTD), of AZD1208 in AML and solid tumours. Secondary objectives were to evaluate the pharmacokinetics, pharmacodynamics (PD) and preliminary efficacy of AZD1208.Sixty-seven patients received treatment: 32 in the AML study over a 120-900 mg dose range, and 25 in the solid tumour study over a 120-800 mg dose range. Nearly all patients (98.5%) in both studies experienced adverse events, mostly gastrointestinal (92.5%). Dose-limiting toxicities included rash, fatigue and vomiting. AZD1208 was not tolerated at 900 mg, and the protocol-defined MTD was not confirmed. AZD1208 increased CYP3A4 activity after multiple dosing, resulting in increased drug clearance. There were no clinical responses; PD analysis showed biological activity of AZD1208.Despite the lack of single-agent clinical efficacy with AZD1208, PIM kinase inhibition may hold potential as an anticancer treatment, perhaps in combination with other agents.

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
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 Advanced Solid Tumor not applicable AZD1208 Phase I Actionable In a Phase I trial, AZD1208 treatment was tolerated and demonstrated activity in pharmacodynamic studies, resulted in stable disease for 6 weeks or longer as best objective response in 48% (13/27) of evaluable patients with advanced solid tumor (PMID: 29765150; NCT01588548). 29765150
Unknown unknown acute myeloid leukemia no benefit AZD1208 Phase I Actionable In a Phase I trial, AZD1208 treatment was tolerated and demonstrated activity in pharmacodynamic studies, but resulted in no clinical response (0/32) in patients with acute myeloid leukemia (PMID: 29765150; NCT01489722). 29765150
Unknown unknown prostate cancer not applicable AZD1208 Case Reports/Case Series Actionable In a Phase I trial, AZD1208 treatment resulted in considerable decrease of PSA levels in a patient with prostate cancer (PMID: 29765150; NCT01588548). 29765150