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 (25324140)
Authors Smith DC, Eisenberg PD, Manikhas G, Chugh R, Gubens MA, Stagg RJ, Kapoun AM, Xu L, Dupont J, Sikic B
Title A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 20
Issue 24
Date 2014 Dec 15
URL
Abstract Text This phase I trial evaluated the safety, pharmacokinetics, and pharmacodynamics of demcizumab (OMP-21M18), a humanized IgG2 mAb targeting the Notch ligand DLL4 in adult patients with advanced malignancies.Standard 3+3 design, with demcizumab 0.5, 1, 2.5, or 5 mg/kg weekly or 2.5, 5, or 10 mg/kg every other week, with an expansion cohort at 10 mg/kg every other week. Dose-limiting toxicities (DLT) were assessed during the first 28 days.Fifty-five patients received demcizumab (15 weekly, 18 every other week, 21 expansion cohort, 1 loading dose). No more than one DLT was seen at any dose level. The MTD was not reached for either schedule. Treatment-related adverse events occurring in >10% of patients were hypertension or blood pressure increased (47%), fatigue (31%), anemia (22%), headache (20%), nausea (13%), hypoalbuminemia (11%), dizziness (11%), and dyspnea (11%). One patient dosed at 2.5 mg/kg developed reversible right-sided heart failure after 63 days on treatment and 4 dosed at 10 mg/kg developed congestive heart failure after ≥98 days on treatment. Five patients were hospitalized with bleeding episodes (2 episodes of tumor-associated bleeding). Sixteen of 25 (64%) evaluable patients at 10 mg/kg had evidence of stabilization of disease or response.Demcizumab was generally well tolerated at doses ≤5 mg weekly with disease stabilization and decreases in tumor size demonstrating antitumor activity. Hypertension was the most common adverse event that was clearly related to treatment. Prolonged administration was associated with an increased risk of congestive heart failure.

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
Demcizumab Demcizumab 3 2
Drug Name Trade Name Synonyms Drug Classes Drug Description
Demcizumab OMP-21M18|anti-delta-like 4 monoclonal antibody OMP-21M18 DLL4 Antibody 6 Demcizumab (OMP-21M18) is a monoclonal antibody that binds DLL4 and prevents its interaction with Notch receptors, thereby inhibiting pathway activation and tumor growth (PMID: 19664991, PMID: 25324140, PMID: 32037195).
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 Demcizumab Phase I Actionable In a Phase I trial, treatment with Demcizumab (OMP-21M18) demonstrated safety and preliminary efficacy in patients with advanced solid tumors (PMID: 25324140). 25324140
Unknown unknown colorectal cancer not applicable Demcizumab Phase I Actionable In a Phase I trial, treatment with Demcizumab (OMP-21M18) resulted in downregulation of Notch target genes and demonstrated preliminary efficacy in patients with advanced solid tumors, with reductions in tumor size in patients with several tumor types, including colorectal cancer (PMID: 25324140). 25324140