Phase II Study of Iniparib with Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma

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 radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM). Experimental Design: Adults meeting eligibility criteria were enrolled in this prospective, single arm, open-label multi-institution phase II trial with median overall survival (mOS) compared to a historical control as the primary objective. A safety run-in component of RT+TMZ+iniparib (n=5) was followed by an efficacy study (n=76) with the recommended phase II doses of iniparib (8.0 mg/kg IV twice/week with RT + daily TMZ followed by 8.6 mg/kg IV twice/week with 5/28 day TMZ). 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%CI: 17-24) and the hazard rate 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 (AE) occurred in 27% of patients; nine patients had AEs requiring drug discontinuation including: infusion-related reaction, rash, gastritis, increased liver enzymes, and thrombocytopenia. Conclusions: Iniparib is well tolerated with RT and TMZ in patients with newly diagnosed GBM at up to 17.2mg/kg weekly. The primary objective of improved mOS compared with historical a control was met, indicating potential antitumor activity of iniparib in this setting. Dosing optimization (frequency and sequence) is needed prior to additional efficacy studies.

https://ift.tt/2Lf4fDB