5551 Background: Tasisulam-sodium (TASI) is a novel, highly albumin-bound small molecule that induces tumor cell apoptosis and has antiangiogenic activity. This phase 1b study was designed as a dose-finding study for TASI in combination with liposomal doxorubicin (DX) in patients (pts) with advanced solid tumors, followed by a dose-confirmation phase in platinum-resistant DX-naïve ovarian cancer (OvCa) pts. However, the study was stopped early for business reasons. Nonetheless, the dataset allowed partial characterization of the safety and antitumor activity of TASI + DX among OvCa pts who achieved an albumin-corrected exposure (AUCalb) within a hypothesized therapeutic range identified in phase II monotherapy trials. Methods: In the dose-escalation phase (3+3 schema), pts received TASI (escalating Cmax targets of 300-380 μg/mL, 2-h IV) plus DX (40 mg/m2, 1-h IV) every 28 days. Pharmacokinetic and safety analyses identified an AUCalb target of 3500 h*μg/mL for the dose-confirmation phase. We analyzed data for OvCa pts from both phases who achieved TASI AUCalbof 1200-6400 h*μg/mL in cycle 1. Results: Of the 13 OvCa pts who completed the dose-escalation phase and 6 OvCa pts who completed the dose-confirmation phase, 10 had AUCalbof 1200-6400 h*μg/mL in cycle 1. For these pts, the most common possibly drug-related Grade 3-4 adverse event was neutropenia (see table). Although no pt achieved complete response, 2 pts achieved partial response. Data from the other OvCa pts will also be presented. Conclusions: The early closure of the study did not allow complete assessment of TASI in combination with DX; however, acceptable tolerability and some antitumor activity were observed for OvCa pts with TASI AUCalbwithin the hypothesized therapeutic range. Clinical trial information: NCT01214668. [Table: see text]
Pre-Clinical Dose Escalation Studies Establish a Therapeutic Range for U7snRNA-Mediated DMD Exon 2 Skipping
