RT Journal Article
SR Electronic
T1 Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 1929
OP 1936
DO 10.1158/1078-0432.CCR-16-1272
VO 23
IS 8
A1 Segal, Neil H.
A1 Logan, Theodore F.
A1 Hodi, F. Stephen
A1 McDermott, David
A1 Melero, Ignacio
A1 Hamid, Omid
A1 Schmidt, Henrik
A1 Robert, Caroline
A1 Chiarion-Sileni, Vanna
A1 Ascierto, Paolo A.
A1 Maio, Michele
A1 Urba, Walter J.
A1 Gangadhar, Tara C.
A1 Suryawanshi, Satyendra
A1 Neely, Jaclyn
A1 Jure-Kunkel, Maria
A1 Krishnan, Suba
A1 Kohrt, Holbrook
A1 Sznol, Mario
A1 Levy, Ronald
YR 2017
UL http://clincancerres.aacrjournals.org/content/23/8/1929.abstract
AB Purpose: Urelumab is an agonist antibody to CD137 with potential application as an immuno-oncology therapeutic. Data were analyzed to assess safety, tolerability, and pharmacodynamic activity of urelumab, including the dose selected for ongoing development in patients with advanced solid tumors and lymphoma.Experimental Design: A total of 346 patients with advanced cancers who had progressed after standard treatment received at least one dose of urelumab in one of three dose–escalation, monotherapy studies. Urelumab was administered at doses ranging from 0.1 to 15 mg/kg. Safety analyses included treatment-related and serious adverse events (AEs), as well as treatment-related AEs leading to discontinuation and death, with a focus on liver function test abnormalities and hepatic AEs.Results: Urelumab doses between 1 and 15 mg/kg given every 3 weeks resulted in a higher frequency of treatment-related AEs than 0.1 or 0.3 mg/kg every 3 weeks. Dose was the single most important factor contributing to transaminitis development, which was more frequent and severe at doses ≥1 mg/kg. At the MTD of 0.1 mg/kg every 3 weeks, urelumab was relatively well tolerated, with fatigue (16%) and nausea (13%) being the most common treatment-related AEs, and was associated with immunologic and pharmacodynamic activity demonstrated by the induction of IFN-inducible genes and cytokines.Conclusions: Integrated evaluation of urelumab safety data showed significant transaminitis was strongly associated with doses of ≥1 mg/kg. However, urelumab 0.1 mg/kg every 3 weeks was demonstrated to be safe, with pharmacodynamic activity supporting continued clinical evaluation of this dose as monotherapy and in combination with other immuno-oncology agents. Clin Cancer Res; 23(8); 1929–36. ©2016 AACR.