Interim Phase II Results Demonstrate Efficacy of PB272 in Combination with Temsirolimus in HER2+ Metastatic Breast Cancer
LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NYSE: PBYI), a development stage
biopharmaceutical company, announced that interim results from an
ongoing Phase II clinical trial of Puma's investigational drug PB272
(neratinib) were presented at the 2014 CTRC-AACR San Antonio Breast
Cancer Symposium (SABCS) that is currently taking place in San Antonio,
Texas. The trial was supported by the National Comprehensive Cancer
Network®, ASCO's Young Investigator Award, Susan G. Komen for the Cure®,
and the Terri Brodeur Breast Cancer Foundation. The presentation is
further detailed below.
The trial was conducted as a Phase I/II trial of PB272 given in
combination with the anticancer drug temsirolimus in patients with
HER2-positive metastatic breast cancer. The Phase I portion of the
trial, which was reported previously, determined that the maximum
tolerated dose was 240 mg of neratinib daily with 8 mg of temsirolimus
weekly and the dose limiting toxicity was diarrhea. The Phase II portion
of the study was conducted in two cohorts. The first cohort, referred to
as the Maximum Tolerated Dose (MTD) cohort, received 240 mg of neratinib
daily with 8 mg of temsirolimus weekly. This cohort of patients received
low dose loperamide (4 mg per day) prophylactically in order to reduce
the neratinib related diarrhea. The second cohort of patients, referred
to as the Dose Escalation cohort (DE cohort), received 240 mg of
neratinib daily and initially received 8 mg of temsirolimus weekly. This
cohort of patients received high dose loperamide (16 mg per day
initially) prophylactically in order to reduce the neratinib related
diarrhea. If patients in the DE cohort had no tolerability issues with
the combination of neratinib and temsirolimus given at 8 mg per week
during the first cycle of treatment, patients in this DE cohort were
allowed to dose escalate the temsirolimus to 15 mg per week for the
remainder of the study. Patients in both cohorts in the study received a
median of 3 prior regimens in the metastatic setting (range 1-8 prior
regimens) before entering the trial. The 37 patients in the MTD cohort
were enrolled at 3 centers in the United States and the 45 patients in
the DE cohort were enrolled at 8 centers in the United States, Europe
and Asia.
The interim safety results of the study showed that the most frequently
observed adverse event for the patients who received the combination of
neratinib plus temsirolimus was diarrhea. For the 37 patients in the MTD
cohort, who received low dose loperamide prophylactically, 12 patients
(32%) experienced grade 3 diarrhea. For the 41 patients in the DE
cohort, who received high dose loperamide prophylactically and were
allowed to dose escalate the temsirolimus dose, 7 patients (17%)
reported grade 3 diarrhea. 4 (57%) of the 7 patients in the DE cohort
who experienced grade 3 diarrhea were not compliant with the high dose
loperamide prophylaxis. There are 4 patients in the DE cohort who did
not yet have safety data reported and are therefore not included in the
safety population. For the patients in the DE cohort, thus far 47% of
the patients have been able to dose escalate from 8 mg per week of
temsirolimus to 15 mg per week of temsirolimus.
The interim efficacy results from the trial showed that for the 37
patients in the MTD cohort, 11 patients (30%) experienced a partial
response (PR). The median duration of response for this cohort of
patients was 3.0 months and the median progression free survival was 4.8
months. For the 37 evaluable patients in the DE cohort, the efficacy
results from the trial demonstrated that 11 patients (30%) experienced a
partial response (PR). The median duration of response for this cohort
of patients was 7.4 months and the median progression free survival is
not yet mature. There are a total of 18 patients currently on active
treatment in the trial. 8 of the 17 active patients in the DE cohort
have not yet had tumor assessments.
Alan H. Auerbach, Chief Executive Officer and President of Puma
Biotechnology, said, "We continue to be pleased with the data on the
combination of PB272 with temsirolimus. This interim data continues to
demonstrate strong antitumor activity in a heavily pretreated population
and compares favorably to what would typically be seen for other
treatment options for patients in this setting. We look forward to
following the remaining patients on study to completion of the trial and
advancing the combination of PB272 and temsirolimus into Phase III
trials in 2015."
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, including
statements regarding plans with respect to clinical 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, 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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