Combined Inhibition of mTORC1 with Temsirolimus and HER2 with Neratinib: A Phase I/II Study in Patients with Metastatic HER2-Amplified or Triple-Negative Breast Cancer

The Phase I/II clinical trial of PB272 given in combination with the chemotherapy drug temsirolimus was conducted at Memorial Sloan-Kettering Cancer Center.  The trial was sponsored by Pfizer and the Phase I results of this trial were previously presented last year.  The Phase II portion of the study, presented at this symposium, enrolled patients with either HER2+ metastatic breast cancer and disease progression on trastuzumab or with triple negative breast cancer.  Patients in the study received a median of 3 prior cytotoxic regimens (range 1-12 prior regimens).  Patients in the HER2+ cohort of the trial received a median of 2 prior trastuzumab containing regimens (range 1-9 prior regimens).  Patients were administered PB272 at a dose of 240 mg per day in combination with temsirolimus given at a dose of 8 mg weekly.

The results of the study presented showed that the combination of PB272 and temsirolimus had acceptable tolerability.  The most frequently observed severe adverse events for the 20 patients evaluable for safety were grade 3 diarrhea (10% of patients), grade 3 hyperglycemia (5%), mucositis (5%), leukopenia (5%), and fatigue (5%). The efficacy results from the trial showed that for the 15 patients with HER2+ disease, 9 (60%) patients experienced a partial response and 1 (7%) patient experienced stable disease for greater than 6 months, which translates to a clinical benefit rate of 67%.  Patients who experienced a partial response to the combination of neratinib plus temsirolimus demonstrated a maximum change in the size of their target lesions of between 33% and 83%.  None of the 5 patients with triple negative breast cancer demonstrated a partial response or stable disease for greater than 6 months.

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are pleased with the PB272 data that has been presented at the San Antonio Breast Cancer Symposium.  The combination of PB272 given in combination with capecitabine shows strong evidence of antitumor activity in second and third line HER2+ metastatic patients, which we believe could position the drug well compared to other agents currently used to treat second and third line disease.  In addition, the data on the combination of PB272 in combination with temsirolimus demonstrates intriguing antitumor activity in a heavily pretreated population.  We look forward to continuing to study both of these combinations as we advance PB272 into further development in the HER2+ metastatic breast cancer population." 

SOURCE Puma Biotechnology, Inc.