19 December 2018 - - US-based biopharmaceutical company Puma biotechnology, Inc. (NASDAQ: PBYI) has received top line results from the Phase III NALA trial of the company's lead drug candidate PB272 (neratinib) in patients with HER2-positive metastatic breast cancer who have failed two or more prior lines of HER2-directed treatments (third-line disease) in the setting of metastatic disease, the company said.

The Phase III NALA trial is a randomized controlled trial of neratinib plus capecitabine versus Tykerb(lapatinib) plus capecitabine in patients with third-line HER2-positive metastatic breast cancer.

This trial enrolled 621 patients who were randomized to receive either neratinib plus capecitabine or lapatinib plus capecitabine.

The trial was conducted globally at sites in North America, Europe, Asia-Pacific and South America. The co-primary endpoints of the trial are centrally confirmed progression free survival and overall survival.

An alpha level of 1% was allocated to the PFS and 4% allocated to OS. The study was to be considered positive if either of the co-primary endpoints was positive.

Puma reached agreement with the US Food and Drug Administration under a Special Protocol Assessment for the design of the Phase III clinical trial and the European Medicines Agency also provided follow-on scientific advice consistent with that of the FDA regarding the company's Phase III trial design and endpoints used in the trial.

For the primary analysis of centrally confirmed PFS, treatment with neratinib plus capecitabine resulted in a statistically significant improvement in centrally confirmed PFS (p=0.0059) compared to treatment with lapatinib plus capecitabine.

For the primary analyses of OS, neratinib plus capecitabine resulted in an improvement in OS that did not achieve statistical significance but trended positively in favor of the neratinib plus capecitabine arm of the study (p=0.21).

For the secondary endpoint of time to intervention for symptomatic central nervous system disease (also referred to as brain metastases), the results of the trial showed that treatment with neratinib plus capecitabine led to an improvement over the combination of lapatinib plus capecitabine (p=0.043).
The safety profile of neratinib in the Phase III NALA study was consistent with previous clinical trials of neratinib.

Full results of the trial will be submitted to health authorities around the world, including the US Food and Drug Administration and European Medicines Agency. Results of the trial will be submitted for presentation at a major medical conference in 2019.

Puma biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialisation of innovative products to enhance cancer care.

Puma in-licenses the global development and commercialization rights to three drug candidates -- PB272 (neratinib, oral), PB272 (neratinib, intravenous) and PB357.

Neratinib, oral was approved by the US Food and Drug Administration in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as Nerlynx (neratinib) tablets.

Nerlynx was granted marketing authorization by the European Commission for the extended adjuvant treatment of hormone receptor-positive HER2-positive early stage breast cancer in September 2018. Nerlynx is a registered trademark of Puma biotechnology, Inc.