LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company,
announced that updated interim results from an ongoing Phase II clinical
trial of Puma's investigational drug PB272 (neratinib), given as
monotherapy and in combination with the anticancer drug fulvestrant,
were presented at the 2016 CTRC-AACR San Antonio Breast Cancer Symposium
(SABCS) that is currently taking place in San Antonio, Texas. The
presentation entitled “Neratinib plus fulvestrant for ERBB2 mutant, HER2
non-amplified, estrogen receptor-positive, metastatic breast cancer:
Preliminary analysis from the Phase II SUMMIT trial” was presented as a
poster discussion by Dr. David Hyman, Director, Developmental
Therapeutics at Memorial Sloan Kettering Cancer Center.
Interim results from this trial were previously presented at the 2015
SABCS and included patients who were treated with neratinib monotherapy
for metastatic breast cancer and whose tumors have a HER2 mutation. The
presentation also discussed that a bidirectional cross-talk between
hormone receptor and HER2 signaling pathways could lead to endocrine
resistance due to activated HER2 signaling and ER-mediated tumor
proliferation as a potential resistance mechanism to sustained HER2
inhibition. Preclinical xenograft data has demonstrated that the
combination of an anti-estrogen with neratinib results in enhanced
anti-tumor activity in preclinical models of estrogen receptor
positive/HER2-positive breast tumors. Based on this, the SUMMIT study
was amended to allow for the combination of neratinib plus fulvestrant
in eligible postmenopausal hormone receptor-positive breast cancer
patients. The presentation at SABCS included an update on both the
neratinib monotherapy cohort and the neratinib plus fulvestrant cohort.
In the study, patients with HER2 mutant metastatic breast cancer were
enrolled and received 240 mg of neratinib daily either as monotherapy or
in combination with fulvestrant. All patients received loperamide (16 mg
per day initially) prophylactically for the first cycle of treatment in
order to reduce the neratinib-related diarrhea. For the 25 patients in
the group who received neratinib monotherapy, 23 patients (92%) had
HER2-negative disease, 19 patients (76%) were hormone receptor positive
(estrogen receptor or progesterone receptor positive), and patients had
received a median of 4 prior lines of therapy in the metastatic setting
(range 0-8 prior regimens) before entering the trial. For the 17
patients in the trial who received neratinib plus fulvestrant, 15
patients (88%) had HER2-negative disease, 17 patients (100%) were
hormone receptor positive (estrogen receptor or progesterone receptor
positive), and patients had received a median of 4 prior lines of
therapy in the metastatic setting (range 1-7 prior regimens) before
entering the trial.
The interim efficacy results from the trial showed that for the 24
efficacy evaluable patients in the neratinib monotherapy cohort, 8
patients (33.3%) experienced an objective response, which included 3
patients with a complete response and 5 patients with partial responses.
At week 8, 8 patients (33.3%) achieved an objective response, with 2
patients achieving a complete response and 6 patients achieving a
partial response The secondary endpoints of the trial included confirmed
objective response (complete response or partial response), clinical
benefit rate and progression free survival (PFS). The results of the
trial showed that 6 patients (25%) had a confirmed objective response,
10 patients (41.7%) demonstrated clinical benefit and the median
progression free survival was 3.5 months.
For the 12 efficacy evaluable patients in the neratinib plus fulvestrant
cohort, 7 patients (58.3%) experienced an objective response, which
included 2 patients with a complete response and 5 patients with partial
responses. At week 8, 5 patients (41.7%) achieved an objective response,
with 2 patients achieving a complete response and 3 patients achieving a
partial response. The secondary endpoints of the trial included
confirmed objective response (complete response or partial response),
clinical benefit rate and progression free survival (PFS). The results
of the trial showed that 3 patients (25%) had a confirmed objective
response, 7 patients (58.3%) demonstrated clinical benefit and the
median progression free survival was 3.7 months. The progression free
survival data may not be mature in the neratinib plus fulvestrant cohort
as 4 of the 12 efficacy evaluable patients are continuing to receive
study treatment without disease progression and an additional 5 patients
have not yet had an assessment for efficacy.
The interim safety results of the study showed that the most frequently
observed adverse event was diarrhea. For the 25 patients enrolled in the
neratinib monotherapy arm, 6 patients (24%) reported grade 3 diarrhea.
The median duration of grade 3 diarrhea for the patients in the
neratinib monotherapy cohort was 1 day. No patient in the neratinib
monotherapy cohort has permanently discontinued neratinib due to
diarrhea and 5 patients (20%) have temporarily discontinued neratinib
due to diarrhea and then restarted after the diarrhea subsided. For the
17 patients enrolled in the neratinib plus fulvestrant cohort, 2 of 17
patients (12%) experienced grade 3 diarrhea. The median duration of
grade 3 diarrhea was 1 day and typically occurred during the first cycle
of treatment. No patient (0%) in the neratinib plus fulvestrant cohort
permanently discontinued neratinib due to diarrhea and 2 patients (12%)
temporarily discontinued neratinib due to diarrhea and then restarted
after the diarrhea subsided.
Dr. David Hyman, Director, Developmental Therapeutics at Memorial Sloan
Kettering Cancer Center and principal investigator of the trial, stated,
“Neratinib showed promising signs of clinical activity both as a single
agent and in the patients treated with the combination of neratinib plus
fulvestrant in this preliminary analysis of pre-treated HER2 mutant
breast cancer patients. The safety profile of the drug was manageable
and the diarrhea was not treatment-limiting with appropriate prophylaxis
and management. We look forward to completing the ongoing neratinib plus
fulvestrant cohort and moving this combination forward into future
clinical development.”
Alan H. Auerbach, Chief Executive Officer and President of Puma
Biotechnology, said, “We are very pleased with the preliminary activity
seen with neratinib, both alone and in combination with fulvestrant in
this cohort of patients with HER2 mutated breast cancer. We look forward
to the completion of the trial and further development of the
combination of neratinib and fulvestrant.”
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 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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