LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company,
announced that results from a randomized Phase II clinical trial of
Puma's investigational drug PB272 (neratinib) in the neoadjuvant
treatment of locally advanced HER2-positive breast cancer were presented
at the 2015 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) that
is currently taking place in San Antonio, Texas. The presentation
entitled "NSABP FB-7: A Phase II Randomized Trial Evaluating Neoadjuvant
Therapy Regimens with Weekly Paclitaxel plus Trastuzumab or Neratinib or
Trastuzumab and Neratinib Followed by Doxorubicin and Cyclophosphamide
with Postoperative Trastuzumab in Women with Locally Advanced
HER2-Positive Breast Cancer" will be presented today at the poster
discussion session. This trial was sponsored by the NSABP Foundation,
Inc.
The FB-7 trial is a randomized Phase II clinical trial for women with
HER2-positive locally advanced stage IIB-IIIC invasive breast cancer.
Patients were randomly assigned to trastuzumab (T) or neratinib (N) or
the combination (T+N) with weekly paclitaxel (P) followed by standard
doxorubicin and cyclophosphamide chemotherapy (AC) administered prior to
surgery. 126 U.S., Canadian, and European patients were randomly
assigned to Arm 1 (T+P followed by AC), Arm 2 (N+P followed by AC) or
Arm 3 (T+N+P followed by AC). The primary endpoint of the trial is
pathological complete response rate (pCR) in the breast and lymph nodes.
Tumor tissue was collected on patients at the time of diagnosis. This
tissue will be analyzed for several biomarkers including AKT, cMET,
EGFR, ESR-alpha, HER2, HER3, HER4, p95 HER2 and PI3K and intrinsic
subtypes. A key secondary endpoint of this trial is the molecular and
genetic correlates of response for each of these biomarkers. The
analysis of these biomarkers is ongoing and will be presented at a
medical meeting in 2016.
For the intent-to-treat patient population (hormone receptor positive
(HR+) and hormone receptor negative (HR-)), the pCR rate for Arm 1 was
38.1%, for Arm 2 was 33.3% and for Arm 3 was 50.0%. For the HR+
patients, the pCR rate for Arm 1 was 29.6%, for Arm 2 was 27.6% and for
Arm 3 was 30.4%. For the HR- patients, the pCR rate for Arm 1 was 57.1%,
for Arm 2 was 46.2% and for Arm 3 was 73.7%.
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Pathological Complete Response Rate (pCR, breast and lymph
nodes)
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Arm
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Arm 1 (T)
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Arm 2 (N)
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Arm 3 (N+T)
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Intent-to-Treat Population
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38.1%
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33.3%
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50.0%
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HR+ Patients
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29.6%
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27.6%
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30.4%
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HR- Patients
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57.1%
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46.2%
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73.7%
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The most frequently observed severe adverse event in the two neratinib
treated arms of the trial (Arm 2 and Arm 3) was diarrhea. In the first
19 patients treated in Arm 2 of the trial, high dose loperamide (16 mg
per day initially) as primary prophylaxis was not given to prevent the
neratinib-related diarrhea. In this subset of patients the grade 3
diarrhea rate was 42% (8/19). In the next 10 patients treated in Arm 2
and the first 20 patients treated in Arm 3, high dose primary
prophylaxis (16 mg per day initially) with loperamide was given during
the initial two weeks of the first cycle of treatment. Using two weeks
of intensive loperamide prophylactically, the grade 3 diarrhea rate in
Arm 2 was 30% (3/10) and the grade 3 diarrhea rate in Arm 3 was 35%
(7/20). In the next 13 patients in Arm 2 and 22 patients in Arm 3, high
dose prophylaxis (16 mg per day initially) was given for the entire
first cycle of treatment (4 weeks). The grade 3 diarrhea rate was 15%
(2/13) in Arm 2 and 23% (5/22) in Arm 3.
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Diarrhea
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No
Prophylaxis
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2-week Prophylaxis
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4-week Prophylaxis
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Arm
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Arm 2 (N)
(n=19)
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Arm 2 (N)
(n=10)
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Arm 3 (N+T)
(n=20)
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Arm 2 (N)
(n=13)
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Arm 3 (N+T)
(n=22)
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Grade 3 Diarrhea
(All Cycles)
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8 (42%)
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3 (30%)
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7 (35%)
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2 (15%)
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5 (23%)
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Dr. Samuel Jacobs, Emeritus Clinical Professor in the Department of
Medicine, University of Pittsburgh School of Medicine, and the Director
of Medical Affairs for the NSABP Foundation, Inc., said, "We are pleased
to see the promising clinical activity of neratinib in combination with
trastuzumab as measured by pCR rates in the hormone receptor negative
patients. We look forward to completing the biomarker analysis to
determine which patients may derive the greatest benefit from this dual
anti-HER2 therapy.”
Alan H. Auerbach, Chief Executive Officer and President of Puma
Biotechnology, said, "We are pleased to complete this neoadjuvant trial
of neratinib, both as a single agent and as a dual HER2 therapy in
combination with trastuzumab. The results of the biomarker analysis
should help us to determine the best path forward for neratinib in the
neoadjuvant treatment of HER2 positive early stage breast cancer."
About Puma Biotechnology
Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on
the acquisition, development and commercialization of innovative
products to enhance cancer care. The Company aims to acquire proprietary
rights to these products, by license or otherwise, fund their research
and development and bring the products to market. The Company is
initially focused on the development of PB272 (oral neratinib), a potent
irreversible tyrosine kinase inhibitor, for the treatment of patients
with HER2-positive breast cancer and patients with non-small cell lung
cancer, breast cancer and other solid tumors that have a HER2 mutation.
Further information about Puma Biotechnology can be found at www.pumabiotechnology.com.
Forward-Looking Statements:
This press release contains forward-looking statements, including, but
not limited to, statements regarding the development of our drug
candidates and the anticipated timing of various clinical trials and the
announcement of data relative to these trials. All forward-looking
statements included in this press release 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, and actual outcomes and results
could differ materially from these statements due to a number of
factors, which include, but are not limited to, the fact that the
Company has no product revenue and no products approved for marketing;
the Company’s dependence on PB272, 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; the Company’s dependence on licensed intellectual property;
and the other risk factors disclosed in the periodic reports filed by
the Company with the Securities and Exchange Commission from time to
time, including the Company’s Annual Report on Form 10-K for the
year ended December 31, 2014 and any subsequently filed Quarterly
Reports on Form 10-Q and Current Reports on Form 8-K. 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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