Puma Biotechnology, Inc. (OTCBB: PBYI), a development stage biopharmaceutical company, announced that results from an ongoing Phase I clinical trial of its lead drug candidate PB272 (neratinib) given in combination with the anticancer drugs paclitaxel and trastuzumab in patients with metastatic HER-2 positive breast cancer were presented in a poster presentation at the American Society of Clinical Oncology (ASCO) 2012 Annual Meeting. This trial was sponsored by the National Surgical Adjuvant Breast and Bowel Project (NSABP), a clinical trials cooperative group supported by the National Cancer Institute (NCI).
A phase I dose-escalating study evaluating weekly paclitaxel with neratinib and trastuzumab in women with metastatic HER-2 positive breast cancer, NSABP FB-8.
The goal of the Phase I clinical trial was to determine the maximum tolerated dose of PB272 that could be given in combination with paclitaxel and trastuzumab to patients with metastatic HER-2 positive breast cancer. The study enrolled patients with confirmed HER-2 positive metastatic or locally advanced breast cancer, and documented disease progression following prior treatment with trastuzumab and taxane chemotherapy. Patients were administered PB272 at doses of 120 mg, 160 mg, 200 mg or 240 mg per day, respectively, in combination with paclitaxel given intravenously at a dose of 80 mg/m 2 on days 1, 8, and 15 of every 28 day cycle until disease progression and trastuzumab administered intravenously weekly using a 4 mg/kg loading dose, then 2 mg/kg weekly until disease progression.
The results of the study showed that of the 120 mg PB272 dose group, 1 of 3 patients developed a dose limiting toxicity (DLT) consisting of grade 3 diarrhea. Three additional patients were enrolled and none experienced DLT. At PB272 dose levels of 160 mg and 200 mg, there were no DLTs. At the PB272 240 mg dose level, 2 of 3 patients had DLTs involving grade 3 diarrhea. The efficacy results from the trial showed that for the 15 evaluable patients, 8 patients showed clinical activity. This included 1 patient with a complete response (CR) as per the RECIST criteria; 1 patient with non-measurable metastatic disease (skin metastases) who demonstrated a complete resolution of disease; 4 patients with a partial response as per the RECIST criteria; and 2 patients with ongoing stable disease, of whom 1 has been ongoing for over 4 months and 1 has been ongoing for over 10 months.