Puma Biotechnology, Inc. Announces Interim Results from an Ongoing Phase II Clinical Trial of Puma's Investigational Drug PB272 at the 2014 CTRC-AACR San Antonio Breast Cancer Symposium
Dec 12 14
Puma Biotechnology, Inc. announced that interim results from an ongoing Phase II clinical trial of Puma's investigational drug PB272 (neratinib) were presented at the 2014 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas. The trial was supported by the National Comprehensive Cancer Network®, ASCO's Young Investigator Award, Susan G. Komen for the Cure®, and the Terri Brodeur Breast Cancer Foundation. The trial was conducted as a Phase I/II trial of PB272 given in combination with the anticancer drug temsirolimus in patients with HER2-positive metastatic breast cancer. The Phase I portion of the trial, which was reported previously, determined that the maximum tolerated dose was 240 mg of neratinib daily with 8 mg of temsirolimus weekly and the dose limiting toxicity was diarrhea. The Phase II portion of the study was conducted in two cohorts. The first cohort, referred to as the Maximum Tolerated Dose (MTD) cohort, received 240 mg of neratinib daily with 8 mg of temsirolimus weekly. This cohort of patients received low dose loperamide (4 mg per day) prophylactically in order to reduce the neratinib related diarrhea. The second cohort of patients, referred to as the Dose Escalation cohort (DE cohort), received 240 mg of neratinib daily and initially received 8 mg of temsirolimus weekly. This cohort of patients received high dose loperamide (16 mg per day initially) prophylactically in order to reduce the neratinib related diarrhea. If patients in the DE cohort had no tolerability issues with the combination of neratinib and temsirolimus given at 8 mg per week during the first cycle of treatment, patients in this DE cohort were allowed to dose escalate the temsirolimus to 15 mg per week for the remainder of the study. Patients in both cohorts in the study received a median of 3 prior regimens in the metastatic setting (range 1-8 prior regimens) before entering the trial. The 37 patients in the MTD cohort were enrolled at 3 centers in the United States and the 45 patients in the DE cohort were enrolled at 8 centers in the United States, Europe and Asia. The interim safety results of the study showed that the most frequently observed adverse event for the patients who received the combination of neratinib plus temsirolimus was diarrhea. For the 37 patients in the MTD cohort, who received low dose loperamide prophylactically, 12 patients (32%) experienced grade 3 diarrhea. For the 41 patients in the DE cohort, who received high dose loperamide prophylactically and were allowed to dose escalate the temsirolimus dose, 7 patients (17%) reported grade 3 diarrhea. 4 (57%) of the 7 patients in the DE cohort who experienced grade 3 diarrhea were not compliant with the high dose loperamide prophylaxis. There are 4 patients in the DE cohort who did not yet have safety data reported and are therefore not included in the safety population. For the patients in the DE cohort, thus far 47% of the patients have been able to dose escalate from 8 mg per week of temsirolimus to 15 mg per week of temsirolimus. The interim efficacy results from the trial showed that for the 37 patients in the MTD cohort, 11 patients (30%) experienced a partial response (PR). The median duration of response for this cohort of patients was 3.0 months and the median progression free survival was 4.8 months. For the 37 evaluable patients in the DE cohort, the efficacy results from the trial demonstrated that 11 patients (30%) experienced a partial response (PR). The median duration of response for this cohort of patients was 7.4 months and the median progression free survival is not yet mature. There are a total of 18 patients currently on active treatment in the trial. 8 of the 17 active patients in the DE cohort have not yet had tumor assessments.
Puma Biotechnology Delays NDA Submission for Breast Cancer Candidate Neratinib to First Quarter of 2016
Dec 4 14
Puma Biotechnology (US) has announced that it will delay the filing for its New Drug Application (NDA) for PB272 (neratinib) until the first quarter of 2016. The firm will file for approval of the candidate as an extended adjuvant treatment for human epidermal growth factor receptor 2- (HER2-) positive early-stage breast cancer. Puma had previously announced that it was anticipating filing the NDA with the US FDA in the first half of 2015 for HER2-positive metastatic breast cancer. Following discussion with the agency, Puma was requested to provide additional data from pre-clinical carcinogenicity studies to support the new indication, in accordance with International Conference on Harmonisation guidelines.
Puma Biotechnology, Inc. - Special Call
Dec 2 14
To discuss the NDA filing timeline update