Puma Biotechnology Presents Results of Biomarker Analysis of Phase II Trial of PB272 in Neoadjuvant Treatment of HER2-Positiv...
December 07 2016 - 6:21PM
Business Wire
Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical
company, announced that a biomarker analysis of the NSABP FB-7
Phase II clinical trial of Puma's investigational drug PB272
(neratinib) was presented at the 2016 CTRC-AACR San Antonio Breast
Cancer Symposium (SABCS) that is currently taking place in San
Antonio, Texas. The presentation entitled “An exploratory
correlative biomarker analysis of NSABP FB-7, a phase II randomized
trial evaluating neoadjuvant therapy with weekly paclitaxel (P)
plus neratinib (N) or trastuzumab (T) or neratinib and trastuzumab
(N+T) followed by doxorubicin and cyclophosphamide (AC) with
postoperative T in women with locally advanced HER2-positive breast
cancer” was presented as a poster presentation. 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 receive 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 was pathological
complete response rate (pCR) in the breast and lymph nodes. The
clinical safety and efficacy data from this trial was presented at
the 2015 SABCS.
A key secondary endpoint of the FB-7 trial was to evaluate
molecular and genetic markers for correlation with response.
Pre-treatment core biopsy samples (n=59) and post treatment
surgical samples (n=17) were obtained from a subset of patients
treated in the FB-7 trial. pCR data were available for 51 patients
from the biomarker cohort. After excluding low tumor content
non-evaluable samples, correlative biomarker analysis was performed
in 42 patients.
Expression levels and the activation status of EGFR/HER2
signaling proteins were investigated. The results of the
phosphorylated HER2 (phosphoHER2) showed that median levels of
phosphoHER2 were higher in the patients who achieved a pCR with
neratinib (n=7) than in the patients who did not achieve a pCR who
received either trastuzumab (n=8, p=0.07) or the combination of
trastuzumab plus neratinib (n=4, p=0.035). There was not a
significant difference in the median levels of phosphoHER2 in the
patients who achieved a pCR with neratinib (n=7), trastuzumab (n=8,
p=0.16) or the combination of trastuzumab plus neratinib (n=4,
p=0.10).
The truncated form of HER2 known as p95HER2 was measured by the
proprietary assay of Pierian Bioscience. p95HER2 represents a
truncated form of the HER2 receptor that lacks the extracellular
trastuzumab binding domain. It is believed to represent a mechanism
of trastuzumab resistance. Median p95HER2 levels were higher in
samples from patients who achieved a pCR with neratinib than in the
patients who did not achieve a pCR who received either trastuzumab
(p=0.027) or the combination of trastuzumab plus neratinib
(p=0.009). There was not a significant difference in the median
levels of p95HER2 in the patients who achieved a pCR with neratinib
(n=7), trastuzumab (n=8, p=0.16) or the combination of trastuzumab
plus neratinib (n=4, p=0.35).
The MammaPrint assay was performed on 59 samples to determine if
there was any imbalance between arms. This assay is a genomic test
that analyzes the activity of 70 genes and then calculates a
recurrence score that is either low risk or high risk. The results
of the MammaPrint showed that the patients in all three arms of the
FB-7 trial were balanced with the median MammaPrint risk score
being similar across arms. There were only three patients with a
MammaPrint low score.
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 results of this exploratory biomarker
analysis which suggests that activation of the HER pathway based on
p95HER2 and phosphoHER2 may correlate with pCR to neratinib.
Further biomarker analysis in additional datasets will be needed to
determine which patients may derive the greatest benefit from
neratinib.”
Alan H. Auerbach, Chief Executive Officer and President of Puma
Biotechnology, said, “We are pleased to complete this biomarker
analysis of neratinib. Further 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 development and commercialization of innovative
products to enhance cancer care. The Company in-licenses the global
development and commercialization rights to three drug
candidates—PB272 (neratinib (oral)), PB272 (neratinib
(intravenous)) and PB357. Neratinib is a potent irreversible
tyrosine kinase inhibitor that blocks signal transduction through
the epidermal growth factor receptors, HER1, HER2 and HER4.
Currently, the Company is primarily focused on the development of
the oral version of neratinib, and its most advanced drug
candidates are directed at the treatment of HER2-positive breast
cancer. The Company believes that neratinib has clinical
application in the treatment of several other cancers as well,
including non-small cell lung cancer and other tumor types that
over-express or have a mutation in HER2. Further information about
Puma Biotechnology can be found at www.pumabiotechnology.com.
Forward-Looking Statements:
This press release contains forward-looking statements,
including statements regarding the development of the Company’s
drug candidates. 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 and current 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, 2015. 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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version on businesswire.com: http://www.businesswire.com/news/home/20161207006393/en/
Puma Biotechnology, Inc.Alan H. Auerbach or Mariann Ohanesian,
+1-424-248-6500info@pumabiotechnology.comir@pumabiotechnology.comorRusso
PartnersDavid Schull or Darren Chia,
+1-212-845-4271david.schull@russopartnersllc.comdarren.chia@russopartnersllc.com
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