KX-ORAX-001: An open label, randomized, multicenter, phase III registrational study to determine the safety, tolerability, and tumor response of oraxol (HM30181A + oral paclitaxel) and its comparability to IV paclitaxel in patients with metastatic breast cancer (MBC)

TPS1116 Background: Paclitaxel is used in multiple cancer types including the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. Due to poor oral absorption, paclitaxel is administered IV and is associated with extra administration costs, inconvenience, burden for the patient, and hypersensitivity reactions to the solubilizing agent Cremophor EL. HM30181A is an intestinal P-gp pump blocker that, when administered orally with paclitaxel capsules (Oraxol), enhances paclitaxel absorption. Interim data from a phase I crossover study showed Oraxol (15-mg HM30181A + 205 mg/m2) 3 days/week had similar AUC0-∞ to IV paclitaxel 80 mg/m2 over 1 hour (Oraxol 5078 ng*hr/mL vs. IV paclitaxel 5652 ng*hr/mL), however the Cmax was substantially lower with Oraxol which may result in lower incidence of neuropathy. In a phase II single arm study of Oraxol in MBC 45.8% and 41.7% of subjects had PR or SD according to RECIST 1.1. Methods: KX-ORAX-001 is a, multi-national open-label, randomized (2:1 Oraxol to IV paclitaxel) phase III registration study comparing Oraxol (15-mg HM30181A + paclitaxel 205 mg/m2 daily x 3 days QW) to IV paclitaxel 175 mg/m2 over 3 hours every third week, in female patients with histologically- or cytologically-confirmed MBC for whom treatment with IV paclitaxel monotherapy has been recommended. The study is powered to demonstrate the superiority of Oraxol on confirmed tumor response rate vs IV Paclitaxel 175mg/m2 q3weeks. The primary efficacy endpoint is confirmed tumor response according to a blinded central radiologist using RECIST 1.1 criteria. The study is designed to enroll approximately 360 evaluable subjects. Two interim DSMB reviews were conducted at approximately 90 and 180 evaluable subjects for safety, futility, and efficacy. Enrollment was initiated Dec 2015 at 45 sites in Central and South America and enrollment has been completed. At final analysis, if there is an approximate difference of ≥10% favoring Oraxol, a p-value of 0.045 [2-tailed] will be achieved. Secondary endpoints are PFS and OS. Clinical trial information: NCT02594371.