P08.032B3-101, GLUTATHIONE PEGYLATED LIPOSOMAL DOXORUBICIN, IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMAS AND BREAST CANCER BRAIN METASTASES

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2014-09, Vol.16 (Suppl 2), p.ii50-ii51
• Main Authors: Brandsma, D., Dieras, V., Altintas, S., Anders, C., Arnedos, M., Gelderblom, H., Soetekouw, P., Jager, A., van Linde, M., Aftimos, P.
• Format: Article
• Language: English
• Subjects: Poster Presentations
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nou174.191

BACKGROUND: Without active delivery across the blood-brain barrier (BBB), efficacy of doxorubicin in intracranial tumors is limited. Glutathione pegylated liposomal doxorubicin (2B3-101) was developed as a brain-targeted chemotherapy. In rats treated with 2B3-101 doxorubicin brain delivery was 5-fold higher as compared to pegylated liposomal doxorubicin (Doxil ® /Caelyx ® ). This resulted in a significant improvement in glioma growth inhibition. In a Phase I dose escalation study in 37 patients with advanced solid tumors and brain metastases (n = 24) or recurrent high grade gliomas (HGG; n = 13), 2B3-101 was well tolerated up to a dose intensity of 15 mg/m 2 /wk, both as single agent and in combination with trastuzumab. Preliminary evidence of anti-tumor activity was observed, including 1 intracranial partial response (PR) and 16 patients with stable disease (SD) after 2 cycles. These results warranted proceeding into a Phase IIa study. METHODS: The purpose of the ongoing Phase IIa study is to evaluate the safety, tolerability and intracranial anti-tumor activity of 2B3-101 in patients with recurrent HGG and the intracranial and extra-cranial anti-tumor activity of 2B3-101 in patients with breast cancer brain metastases (BCBM) (n = 14 per group). Patients with recurrent HGG are treated with 2B3-101 60 mg/m 2 iv q28d while patients with BCBM are treated with 2B3-101 50 mg/m 2 iv q21d, in HER2 positive patients combined with trastuzumab (iv, 6mg/kg, q21d). Results up to March 15 th 2014 are described in this abstract; in October 2014 the complete data set will be presented. RESULTS: To date, 18 patients with HGG and 10 patients with BCBM have been enrolled in the Phase IIa part of the study and have received a total of 35 (range 1-4) and 34 (range 1-7) cycles of 2B3-101, respectively. At both dose regimes, the side effects were consistent with Doxil ® /Caelyx ® and with the earlier Phase I results of 2B3-101. The most common adverse events (AEs) grade ≥2 related to 2B3-101 were: neutropenia (28%), palmar-plantar erythrodysesthesia (PPE) (21%), infusion reactions (21%) and oral mucositis (17%). No CNS and/or cardiac toxicity were reported. 2B3-101 cycles were administered per protocol in 92% of the HGG patients and in 62% of the BCBM patients. The main reasons for dose delays/ reductions were neutropenia (19%) and PPE (69%). The anti-tumor activity was evaluable in 13 patients with HGG and in 9 patients with BCBM. In the HGG cohort, 31% of the patients had SD