ACTR-45. A PHASE IB STUDY EVALUATING THE C-MET INHIBITOR INC280 IN COMBINATION WITH BEVACIZUMAB IN GLIOBLASTOMA MULTIFORME (GBM) PATIENTS Free

The HGF/c-MET pathway is deregulated in cancer affecting tumor cell proliferation, invasion, metastasis and angiogenesis. INC280 is an oral small molecule inhibitor of c-Met. Bevacizumab produces responses in patients with recurrent glioblastoma (rGBM); however this has not translated into a survival benefit. One reason may be the complex interaction of HGF/c-Met with VEGF and its receptors and their role in glioblastoma. This phase Ib study is evaluating INC280+ bevacizumab in patients with rGBM.

Adults with rGBM (progressed during or after ≥ 1st-line therapy, no prior bevacizumab) received INC280 PO BID using a 3+3 dose escalation design plus bevacizumab 10 mg/kg IV on D 1 and 15 of 28-day cycles. INC280 Dose level (DL) 1 = 100mg BID daily; DL2=200mg BID daily; DL3=400mg BID daily. Patients were restaged per RANO criteria every 2 cycles of treatment; patients continued treatment until progressive disease (PD) or unacceptable toxicity.

15 patients have been treated with increasing doses of INC280 in combination with bevacizumab. Data from 6 patients treated at DL 1 and 2 are included. Median age 60 years, all patients received prior chemotherapy; 1 patient also received targeted therapy; 5/6 patients received prior RT and 5/6 patients had surgery. Patients received a median of 3 (range 2–6) treatment cycles. 5 patients discontinued treatment (PD), 1 patient is currently on-study. Most AEs were grade 1 or 2. One treatment-related grade 3 AEs (ALT increase) was reported. Best response was PR in 2 patients, SD in one patient and PD in 2 patients.

The combination of INC280 and bevacizumab is tolerable and no DLTs were observed at the dose levels examined. Additional patient and response data will be provided in the poster.