LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NYSE: PBYI), a development stage
biopharmaceutical company, announced that positive initial data from the
ongoing, open label Phase II clinical trial of its investigational drug
PB272 (neratinib) for the treatment of patients with non-small cell lung
cancer (NSCLC) with HER2 mutations was presented today as a
late-breaking oral presentation at the European Society for Medical
Oncology (ESMO) 2014 Congress, taking place in Madrid, Spain. The
presentation was entitled “Neratinib with or without temsirolimus in
patients with non-small cell lung cancer carrying HER2 somatic
mutations: An international randomized Phase II study.”
In the trial, patients with confirmed stage IIIB or stage IV
NSCLC with documented somatic HER2 mutations were randomized to receive
either oral neratinib monotherapy at a dose of 240 mg per day or the
combination of oral neratinib (at a dose of 240 mg daily) with
intravenous temsirolimus administered at a dose of 8 mg per week. In
order to attempt to reduce the neratinib related diarrhea, high-dose
loperamide prophylaxis (Imodium) was given to all patients in both arms
of the study beginning on day 1 of neratinib dosing. The data presented
in the oral presentation involved a total of 27 patients who completed
the first stage of the trial; 13 of these patients received neratinib
monotherapy and 14 of these patients received the combination of
neratinib plus temsirolimus.
The results of the study showed that the combination of PB272 and
temsirolimus had acceptable tolerability. Historically the most
frequently seen adverse event associated with neratinib has been
diarrhea. In the previous Phase I trial of neratinib plus temsirolimus
(J Clin Oncol 2014) the diarrhea with neratinib was seen to be dose
dependent and its incidence increased with increasing neratinib dosage.
In that Phase I trial, grade 3 or higher diarrhea was seen in
approximately 30% of the patients treated with doses of neratinib that
were 200 mg or higher.
In this Phase II study, all patients received high-dose loperamide in
order to attempt to prevent or reduce the neratinib-related diarrhea.
For the 13 patients enrolled in the neratinib monotherapy arm, 1 (8%)
patient experienced grade 3 diarrhea, and for the 14 patients enrolled
in the combination of neratinib plus temsirolimus arm, 2 (14%) patients
experienced grade 3 diarrhea. There were no grade 4 diarrhea events seen
in the trial. For the 3 patients in the study (1 in the monotherapy arm,
2 in the combination arm) who experienced grade 3 diarrhea, 2 of the 3
patients were not compliant with the loperamide prophylaxis regimen and
were not taking loperamide at the onset of grade 3 diarrhea.
The efficacy results from the trial showed that for the 13 patients in
the trial who received neratinib monotherapy, no patient experienced a
partial response, 7 (54%) patients achieved stable disease and 4 (31%)
patients achieved clinical benefit (defined as a partial response or
stable disease for 12 or more weeks). For the 14 patients who received
the combination of neratinib plus temsirolimus, 3 (21%) patients
experienced a partial response, 11 (79%) patients experienced stable
disease and 9 (64%) patients achieved clinical benefit. The median
progression free survival of the neratinib monotherapy arm was 2.9
months and the median progression free survival of the arm that received
neratinib plus temsirolimus was 4.0 months. Patients continue to be
enrolled in the arm of the trial that is receiving the combination of
neratinib plus temsirolimus.
“We are pleased with the initial results of the Phase II trial with
neratinib in patients with HER2 mutated non-small cell lung cancer,”
said Alan H. Auerbach, Chief Executive Officer and President. “The
activity seen to date in the trial confirms the efficacy signal seen in
the prior Phase I trial and supports future study. This represented our
first clinical trial to implement the high-dose loperamide prophylaxis
from the beginning of the trial in order to reduce the neratinib-related
diarrhea, and we are very pleased with the reductions in grade 3 or
higher diarrhea seen using this prophylaxis in the trial. These results
are consistent with what we are seeing in our other studies that are
utilizing the loperamide prophylaxis to reduce grade 3 or higher
diarrhea with neratinib, which is resulting in an improvement in the
tolerability of the agent.”
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 (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. 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, 2013. 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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