Puma Begins Phase III Development of Neratinib in Breast Cancer

Puma Biotechnology is a Los Angeles-based development stage biopharmaceutical company that has spent the last couple of years focused on the development of its lead drug candidate, neratinib (PB272).

The company was founded in 2010, with Alan H. Auerbach having served as Puma’s chairman of the board, chief executive officer, and president since its inception. Previously, Auerbach served as co-chairman of the Integration Steering Committee at Cougar, the company that was responsible for the development of abiraterone acetate (Zytiga) for the treatment of prostate cancer. In 2011, Puma completed a reverse merger and reached an agreement with Pfizer to license the worldwide commercial rights to the novel therapeutic compound neratinib, which Pfizer had been developing.

Neratinib is a pan-HER inhibitor that blocks signal transduction through the epidermal growth factor receptors, ErbB1 (EGFR), ErbB2 (HER2), and ErbB4 (HER4) kinases. The drug is being explored in the neoadjuvant, adjuvant, and metastatic settings in patients with HER2-positive breast cancer. After Puma acquired the rights to the drug, the company said it wanted to focus its development in patients with HER2-positive breast cancer who have received prior therapy with trastuzumab (Herceptin).

Since that time, several promising clinical trial results involving neratinib have become available. At the 2012 Annual Meeting of the American Society of Clinical Oncology, a phase I dose escalation study found that neratinib could be safely administered with weekly paclitaxel and trastuzumab, with patients who received 160-mg or 200-mg doses of neratinib experiencing no dose-limiting toxicities. Recently, a study was published in the British Journal of Cancer that found that patients with HER2-positive breast cancer who received a combination of neratinib and paclitaxel had a median overall response rate of 73%.

Currently, neratinib is furthest along in a phase III study that launched in June in which the drug, in combination with capecitabine (Xeloda), is being compared with lapatinib plus capecitabine in patients with metastatic HER2- positive breast cancer who have received two or more prior HER2-targeted therapies. The trial will be conducted in more than 150 sites across North America, Europe, and Asia. The enrollment goal is 600 patients, and the study is expected to be completed in 2018. The progression-free survival data obtained from this trial is expected to serve as the basis for a new drug application to the FDA for the accelerated approval of neratinib, and the company entered an agreement with the FDA under a Special Protocol Assessment for the design of the trial.

There are also a number of phase II clinical trials of neratinib currently under way. According to Puma’s pipeline, neratinib is being explored in combination with temsirolimus injection for metastatic breast cancer; as a single agent and in combination with surgical resection for the treatment of breast cancer that has metastasized to the brain; in combination with chemotherapy as a neoadjuvant treatment for breast cancer; and as an oral single agent for HER2-positive breast cancer. Additionally, a phase II trial exploring the efficacy of neratinib with and without temsirolimus for the treatment of non—small cell lung cancer is also recruiting patients.

Neratinib (PB272) Development

Indication

Phase I

Phase II

Phase III

Metastatic Breast Cancer

(combined with capecitabine)

Metastatic Breast Cancer

(combined with temsirolimus)

Metastatic Breast Cancer With Brain Metastases

(single agent/combination)

Neoadjuvant Breast Cancer

(combined with chemotherapy)

HER2-Mutated Breast Cancer

HER2-Mutated Non-Small Cell Lung Cancer

(combination)