Results of a phase Iib active-controlled study with AP 12009 for patients with recurrent or refractory anaplastic astrocytoma

Abstract

2076 Background: High-grade gliomas (HGG) show an overexpression of TGF-beta 2. AP 12009 is a TGF-beta 2 specific inhibitor, which has been successfully tested in phase I/II studies in patients with recurrent or refractory HGG. Methods: The phase IIb study G004 was an international, open-label, randomized, active-controlled, dose-finding study in patients with recurrent or refractory HGG (WHO grades III and IV). Patients were randomized into 3 treatment groups. Main objective was to compare 2 doses of AP 12009 (10 μM=AP-10 or 80 μM=AP-80) and standard chemotherapy (TMZ or PCV) with regard to response rate, survival, and safety. AP 12009 was administered intratumorally by convection-enhanced delivery with up to 11 treatment cycles (7-d-on, 7-d-off / cycle. Results: Here we report on the subpopulation of patients with recurrent AA (WHO grade III, GBM patients see separate abstract). The AP-10 group showed an overall comparable safety profile as the control group. Although there was a higher incidence of SAEs in the AP 12009 groups, these were often procedure-related and mostly reversible. No drug-related SAEs were observed in any of the 3 treatment groups. The current median of survival times was higher in both AP 12009 groups than in the control group with a remarkable survival benefit of AP-10 over chemotherapy of 12.3 months. Furthermore, more individuals in the AP-10 group experienced long-term clinical benefit (CR+PR) and showed significantly more responders after 14 months. Dose finding was achieved, as efficacy and safety results for the AP-10 group were better than those of the AP-80 group. Conclusions: AP 12009 showed a positive risk-benefit profile and demonstrated an excellent potential as single agent for the treatment of recurrent or refractory AA patients, especially for the AP-10 group. A phase III study in patients with recurrent or refractory AA is planned to start in Q2 2008. Treatment group AP-10 (N=12) AP-80 (N=15) Control (N=12) Incidence of SAEs (%) 67 67 25 Related or possibly related 0 0 0 Current median of survival times (months) 34.0 31.7 21.7 Survival rate at 24 months (%) 83 53 42 Overall response rate (CR+PR) at 14 months (%) 42* 20 0* CR=complete response, PR=partial response, * significant difference between AP-10 and control (p<0.05) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Antisense Pharma Antisense Pharma GmbH Antisense Pharma Antisense Pharma GmbH