Oral neratinib: Phase II data

Puma said a neratinib-containing regimen "graduated" from the open-label I-SPY 2 trial based on having a high probability of success in patients with HER2-positive/hormone receptor-negative breast cancer in a Phase III trial. The company said that as far as it knows, the neratinib-containing regimen is the first to graduate from I-SPY 2, which is designed to rapidly and inexpensively develop data to support small Phase III trials of new neoadjuvant therapies for locally advanced breast cancer or to help companies quickly kill ineffective candidates. I-SPY 2 involves an adaptive trial design based on Bayesian predictive probability that a regimen will be statistically superior to standard therapy in an equally randomized 300-patient confirmatory trial. In patients with HER2-positive/hormone receptor-negative breast cancer, oral neratinib plus paclitaxel followed by doxorubicin and cyclophosphamide led to a greater pCR rate, the primary endpoint, vs. standard therapy consisting of paclitaxel plus Herceptin trastuzumab followed by doxorubicin and cyclophosphamide. Puma said the Bayesian probability of superiority for the neratinib-containing regimen compared to standard therapy is 94.7%, or p=0.053. Additionally, the Bayesian predictive probability of showing statistical superiority for the neratinib-containing regimen compared to standard therapy in a 300-patient Phase III trial is 78.1%. There were 115 patients assigned to neratinib in the trial, including 65 patients with HER2-positive breast cancer.

In patients with HER2-positive breast cancer, the neratinib-containing regimen also led to a greater pCR rate vs. standard therapy. The Bayesian probability of superiority for the neratinib-containing regimen in patients with HER2-positive breast cancer compared to standard therapy is 95.3%, or p=0.047. Additionally, the Bayesian predictive probability of showing statistical superiority for the neratinib-containing regimen compared to standard therapy in a 300-patient Phase III trial is 72.5%. Based on the I-SPY 2 data, Puma said neratinib is now eligible for the upcoming Phase III I-SPY 3 trial, which is likely to start next year. Puma said the regimen likely to be evaluated in Phase III testing will be neratinib plus paclitaxel in combination with either Herceptin or Herceptin and Perjeta. Puma has exclusive, worldwide rights to develop and commercialize neratinib from Pfizer. Earlier this year, Puma began a Phase III trial with neratinib as third-line treatment of HER2-positive metastatic breast cancer. Genentech Inc., a unit of Roche (SIX:ROG; OTCQX:RHHBY, Basel, Switzerland), markets Herceptin in the U.S., while Roche markets it elsewhere. ...