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Abstract
PURPOSE:
Iniparib is a purported prodrug causing cell death through intracellular conversion to nitro radical ions. We assessed the efficacy and safety of iniparib with standard radiotherapy and temozolomide in patients with newly diagnosed glioblastoma (GBM).

PATIENTS AND METHODS:
Adults meeting eligibility criteria were enrolled in this prospective, single-arm, open-label multi- institution phase II trial with median overall survival (mOS) compared with a historical control as the primary objective. A safety run-in component of radiotherapy + temozolomide + iniparib (n = 5) was followed by an efficacy study (n = 76) with the recommended phase II doses of iniparib (8.0 mg/kg i.v. twice/week with radiotherapy + daily temozolomide followed by 8.6 mg/kg i.v. twice/week with 5/28-day temozolomide).

RESULTS:
The median age of the 81 evaluable participants was 58 years (63% male). Baseline KPS was ≥ 80% in 87% of participants. The mOS was 22 months [95% confidence interval (CI), 17-24] and the HR was 0.44 (95% CI, 0.35-0.55) per-person-year of follow-up. The 2- and 3-year survival rates were 38% and 25%, respectively. Treatment-related grade 3 adverse events (AEs) occurred in 27% of patients; 9 patients had AEs requiring drug discontinuation including infusion-related reaction, rash, gastritis, increased liver enzymes, and thrombocytopenia.

CONCLUSIONS:
Iniparib is well tolerated with radiotherapy and temozolomide in patients with newly diagnosed GBM at up to 17.2 mg/kg weekly. The primary objective of improved mOS compared with a historical control was met, indicating potential antitumor activity of iniparib in this setting. Dosing optimization (frequency and sequence) is needed prior to additional efficacy studies.

Author information

Blakeley JO1,2, Grossman SA2, Chi AS3, Mikkelsen T4, Rosenfeld MR5, Ahluwalia MS6, Nabors LB7, Eichler A8, Ribas IG9, Desideri S10, Ye X2; Adult Brain Tumor Consortium.
1
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Jblakel3@jhmi.edu.
2
Department of Oncology and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
3
Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, New York.
4
Ontario Brain Institute, Toronto, Ontario, Canada.
5
Institute for Biomedical Research (IDIBAPS)/Hospital Clinic, Barcelona, Spain.
6
Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio.
7
Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama.
8
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
9
Takeda Oncology, Cambridge, Massachusetts.
10
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.