A phase I dose escalation study of SCB01A, a micro-tubular inhibitor with vascular disrupting activity, in patients with advanced solid tumors refractory to standard therapy.

Abstract

2531 Background: SCB01A is a novel anti-microtubular agent with vascular disrupting activity. The Phase I study aimed to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), safety, and pharmacokinetic (PK) profiles of SCB01A in patients with advanced solid tumor. Methods: This was an open-label, phase I clinical trial with a rapid titration followed by a 3 x 3 study design. Eligible patients would receive a 3-hr intravenous infusion of SCB01A, every 21 days as one cycle. All adverse events were classified according to the CTCAE V4.0. DLT was defined as the occurrence of grade 3 with complications and grade 4 hematoloigcal, or ≥grade 3 non-hematological toxicities. Results: From June 2011 to November 2015, a total of 33 eligible patients were enrolled to eight dose levels: 2 mg/m2 (n = 1), 3 mg/m2 (n = 1), 4 mg/m2 (n = 6), 6.5 mg/m2 (n = 9, with 3 additional subjects were recruited for safety concern), 10 mg/m2 (n = 3), 16 mg/m2 (n = 3), 24 mg/m2 (n = 6) and 32 mg/m2 (n = 4). Six episodes of DLTs were observed in 5 patients (each one in dose levels of 4/6.5/24 mg/m2 and two in dose level of 32 mg/m2), including grade 4 blood creatine phosphokinase elevation (4 mg/m2), grade 3 gastric hemorrhage (6.5 mg/m2), grade 2 venous thrombosis (24 mg/m2), grade 3 peripheral neuropathy manifested as weakness of lower limbs, grade 3 aspartate aminotransferase elevation, and grade 3 hypertension (32 mg/m2). The MTD was determined to be 24 mg/m2. Pharmacokinetic profiles revealed a linear AUC-dose response with an average elimination half-life (t1/2) of 2.5 hours. Partial response was observed in one subject with buccal cancer. A total of 57.6% (19/33) subjects had stable disease for at least 2 cycles. Conclusions: SCB01A is safe and tolerable in patients with solid tumor. The MTD of SCB01A is 24 mg/m2 every 21 days, which deserves further development. Clinical trial information: NCT011159522.