Puma Biotechnology, Inc., a development stage biopharmaceutical company,
announced that results from ongoing Phase II clinical trials of Puma's
investigational drug PB272 (neratinib) were presented at the 2011
CTRC-AACR San Antonio Breast Cancer Symposium that is currently taking
place in San Antonio, Texas. These presentations are further detailed
below:
Safety and Efficacy of Neratinib in Combination With Capecitabine
in Patients With ErbB2-positive Breast Cancer
The Phase I/II clinical trial of PB272 given in combination with the
chemotherapy drug capecitabine was conducted at numerous locations in
the United States, Europe and Asia. 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 confirmed ErbB2+ (HER2+) metastatic or locally
advanced breast cancer, and documented disease progression following
prior treatment with trastuzumab and taxane chemotherapy. Patients were
administered PB272 at a dose of 240 mg per day in combination with
capecitabine given at a dose of 1,500 mg/m2 (750 mg/m2 twice daily) on
Days 1 to 14 of each 21-day cycle.
The results of the study showed that the combination of PB272 and
capecitabine had acceptable tolerability. The most frequently observed
severe adverse event in the trial was diarrhea with 26% of the patients
experiencing grade 3/4 diarrhea. The diarrhea was reported to be
transient and managed with antidiarrheal agents and dose modifications.
The efficacy results from the trial showed that for the 61 patients in
the trial who had not been previously treated with the HER2 targeted
agent lapatinib, 7 (11%) patients experienced a complete response, 32
(52%) patients experienced a partial response and 5 (8%) patients
experienced stable disease for greater than 6 months, which translates
to an overall response rate of 64% and a clinical benefit rate of 72%.
In addition, for the 7 patients in the trial who had previously been
treated with lapatinib, 1 (14%) patient experienced a complete response,
3 (43%) patients experienced a partial response and 1 (14%) patient
experienced stable disease for greater than 6 months, which translates
to an overall response rate of 57% and a clinical benefit rate of 71%.
The median progression free survival (PFS) for patients who had not
received prior treatment with lapatinib was 40.3 and the median PFS for
the patients who had received prior lapatinib treatment was 35.9 weeks.
A Phase II, Randomized, Open-label Study of Neratinib Versus
Lapatinib Plus Capecitabine for 2nd/3rd-line Treatment of HER2+ Locally
Advanced or Metastatic Breast Cancer
The Phase II randomized trial of PB272 given as monotherapy versus the
combination of lapatinib given in combination with capecitabine was
conducted at numerous locations in the United States, Europe and Asia.
The trial was sponsored by Pfizer. In the trial, patients who had
confirmed HER2+ metastatic or locally advanced breast cancer and disease
progression following prior treatment with trastuzumab and taxane
chemotherapy were enrolled. Patients were randomized to receive either
PB272 given as monotherapy daily at a dose of 240 mg per day or the
combination of lapatinib given daily at a dose of 1,250 mg per day in
combination with capecitabine given at a dose of 2,000 mg/m2 (1,000
mg/m2 twice daily) on Days 1 to 14 of each 21-day cycle.
The results of the study showed that the most frequently observed severe
adverse events in the trial were diarrhea and palmar-plantar
erythrodysesthesia (PPE, or hand-foot syndrome). More specifically, 28%
of the patients in the neratinib arm of the trial and 10% of the
patients in the lapatinib/capecitabine combination arm of the trial
experienced grade 3/4 diarrhea. No patients in the neratinib arm of the
trial and 14% of the patients in the lapatinib/capecitabine combination
arm of the trial experienced grade 3/4 PPE. The diarrhea with neratinib
was reported to be transient and manageable with antidiarrheal
medications. The efficacy results from the trial showed that for the 117
patients in the neratinib monotherapy arm of the trial, 2% of the
patients experienced a complete response, 27% of the patients
experienced a partial response and 15% of the patients experienced
stable disease for greater than 6 months, which translates to an overall
response rate of 29% and a clinical benefit rate of 44%. For the 116
patients in the trial treated with the combination of lapatinib and
capecitabine, 4% of the patients experienced a complete response, 36% of
the patients experienced a partial response and 23% of the patients
experienced stable disease for greater than 6 months, which translates
to an overall response rate of 40% and a clinical benefit rate of 63%.
The median progression free survival (PFS) for patients in the neratinib
monotherapy arm was 4.5 months and the median PFS for the patients who
had received the combination of lapatinib and capecitabine was 6.8
months.
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."
About Puma Biotechnology
Puma Biotechnology, Inc., is a development stage biopharmaceutical
company that acquires and develops innovative products for the treatment
of various forms of cancer. The Company focuses on in-licensing drug
candidates that are undergoing or have already completed initial
clinical testing for the treatment of cancer and then seeks to further
develop those drug candidates for commercial use. The Company is
initially focused on the development of PB272 (neratinib), an oral
potent irreversible tyrosine kinase inhibitor, for the treatment of
patients with HER2 positive metastatic breast cancer.
Further information about Puma Biotechnology can be found at
www.pumabiotechnology.com.
Forward-Looking Statements: This press release contains
forward-looking statements that involve risks and uncertainties that
could cause the Company's actual results to differ materially from the
anticipated results and expectations expressed in these forward-looking
statements. These statements are based on current expectations,
forecasts and assumptions that are subject to risks and uncertainties,
which could cause actual outcomes and results to differ materially from
these statements. These risks include, among other things, that the
Company has no product revenue and no products approved for marketing,
the Company's dependence on its lead drug candidate, which is still
under development and may never receive regulatory approval, the
challenges associated with conducting and enrolling clinical trials, the
risk that the results of clinical trials may not support the Company's
drug candidate claims, even if approved, the risk that physicians and
patients may not accept or use the Company's products, the Company's
reliance on third parties to conduct its clinical trials and to
formulate and manufacture its drug candidates and the Company's
dependence on licensed intellectual property and various other risks set
forth from time to time in the Company's filings with the Securities and
Exchange Commission, including but not limited to the risks discussed in
the Company's Current Report on Form 8-K filed with the Securities and
Exchange Commission on October 11, 2011 and in its other filings with
the Securities and Exchange Commission. Readers are cautioned not to
place undue reliance on these forward-looking statements, which speak
only as of the date hereof. The Company assumes no obligation to update
these forward-looking statements, except as required by law.
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