LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company,
announced that its drug candidate neratinib was highlighted in three
poster presentations at the American Association for Cancer Research
(AACR) Annual Meeting 2016. The AACR Annual Meeting was held at the
Ernest N. Morial Convention Center in New Orleans from April 16 to April
20.
Abstract Number 298: Amplification of mutant ERBB2
drives resistance to the irreversible kinase inhibitor neratinib in
ERBB2-mutated breast cancer patients.
On Sunday April 17th, preclinical data was presented from
studies performed to identify possible mechanisms of acquired resistance
to neratinib therapy in ERBB2-mutated breast cancers. Data from three
breast cancer patients in the ongoing phase II SUMMIT basket study of
neratinib in ERBB2-mutant cancers who progressed following initial
benefit from neratinib treatment identified a common genomic alteration
in their tumors. More specifically, targeted exome sequencing of
biopsies collected at time of disease progression revealed increased
copy number of the ERBB2-mutant allele. In addition, enhanced receptor
activity in the ERBB2-mutant cells correlated with increased formation
of ERBB2/ERBB3 dimers, activation of the PI3K/AKT pathway and in vivo
tumorigenic potential. Combined ERBB2 and ERBB3 inhibition efficiently
inhibited phosphorylation of ERBB2/ERBB3 and cell proliferation. These
studies indicate that amplification of mutated ERBB2 may promote
increased ERBB2/ERBB3 dimerization, ERBB3 activation, and subsequent
downstream signaling activation and that dual ERBB2/ERBB3 blockade may
be a potential strategy to delay or prevent resistance to neratinib in
ERBB2-mutant breast tumors.
Abstract Number 3140: Differential clonal selection
in tumor tissue and cell-free DNA from a neratinib-treated refractory
breast cancer patient harboring an activating ERBB2 (HER2) mutation.
On Tuesday April 19th, data was presented from a patient who
was part of the ongoing Copenhagen Prospective Personalized Oncology
(CoPPO) research program. This program aims to offer patients with
limited treatment options targeted treatments against actionable driver
mutations that have been identified in circulating cell free DNA in
patients by using whole exome sequencing. The poster presented data from
a patient with metastatic HER2-negative and estrogen receptor
(ER)-positive breast cancer (Luminal A) who had previously been exposed
to seven lines of chemotherapy as well as ER antagonists and aromatase
inhibitors. After examination by whole exome sequencing, an activating
mutation in ERBB2 (S310Y) was found and consequently the patient was
treated with neratinib through a compassionate use program. Neratinib
caused a rapid decrease in the allelic frequency of ERBB2 (S310Y) cell
free DNA after 2 days, with a continuous decline during the next 7 days.
Consistent with this neratinib treatment effect, MRI scans showed
regression of the liver metastases. After 5 months on neratinib, the
patient progressed with the appearance of brain metastases, which were
surgically removed and subject to whole exome sequencing. The ERBB2
mutation observed in the liver metastasis could not be identified in the
brain metastases. However, more than 300 new variants were exclusively
identified in the brain metastases, among these ERBB3 as well as new
PIK3CA, and ESR1 mutations, that were not present in the pre-treatment
cell free DNA samples. In conclusion, neratinib was able to suppress an
activating ERBB2 mutation in a heavily pre-treated ER+ breast cancer
patient. However, refractory tumor clones harboring ERBB3, PIK3CA and
ESR1 mutations developed in brain. The poster indicated that combining
neratinib with fulvestrant or inhibitors of the HER3/PI3K/AKT/mTOR
pathway might prove beneficial to overcome potential resistance
mechanisms to therapy.
Abstract Number 4760: Efficacy of EGFR/HER2
duel-kinase inhibitors in PDX models harboring known and novel
HER2-mutations.
On Wednesday April 20th, preclinical studies to better
understand effects of HER2 mutations were presented. Patient-derived
xenograft (PDX) tumor models representing colorectal, ovary, pancreas
and endometrial cancers were evaluated in vivo, testing the antitumor
activity of neratinib, afatinib, lapatinib, trastuzumab and T-DM1
administered on standard treatment regimens. In vivo treatment with
neratinib or afatinib resulted in tumor growth inhibition in some tested
models including ST022 (HER2G366R/R678Q) ovary and ST204 (HER2A386D)
pancreas and tumor regressions were reported with either agent in the
ST427 (HER2V777L) colorectal line. Neratinib or afatinib were also found
active in one each of four tested endometrial models. Lapatinib,
trastuzumab and T-DM1 were inactive in all tested HER2-mutant models.
The abstracts of the three presentations described above are available
online at: http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=63&DetailItemID=363#.Vusrr-IrKUk.
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 may 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, 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 risk
factors disclosed in the periodic and current reports filed by the
Company with the Securities and Exchange Commission from time to time.
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.
Contact: