- Data published online today in Nature -
LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company,
announced that initial results from the company’s ongoing SUMMIT Phase
II ‘basket’ clinical trial of PB272 (neratinib) in patients with tumors
harboring HER2 or HER3 mutations were published in the journal
Nature
.
The paper, “HER kinase inhibition in patients with HER2- and HER3-mutant
cancers,” appears in the January 31, 2018 online issue at http://nature.com/articles/doi:10.1038/nature25475
and will be published in a future print issue of the journal.
The Phase II SUMMIT trial is a global, multi-histology, open-label,
precision-medicine ‘basket’ study evaluating the safety and efficacy of
neratinib administered daily to patients with a wide variety of solid
tumors with activating HER2 or HER3 mutations. SUMMIT is designed to
evaluate the contributions of both genetic mutation and cancer type on
individual patients’ response to neratinib. Information generated from
the trial will help guide neratinib-based targeted therapy across a
broad spectrum of tumor types with HER2 or HER3 mutations, including
patients with rare tumors who may not otherwise have access to
investigational therapies.
“Publication of the initial SUMMIT data in this prestigious journal
reflects the novelty and quality of this precision-medicine trial
design, as well as the growing understanding that both tumor type and
gene mutations play an important role in individual patients’ response
to cancer therapies such as neratinib,” said Alan H. Auerbach, Puma’s
Chief Executive Officer and President. “The basket trial design utilized
for SUMMIT is enabling researchers to evaluate the clinical potential of
neratinib in multiple cancer types, rather than limiting exploration to
one tumor type at a time. SUMMIT is also significant in that it will
provide the largest body of clinical data to date on the use of an
irreversible pan-HER inhibitor in patients who have solid tumors with
somatic HER2 or HER3 mutations.”
The initial SUMMIT results published in Nature comprise data from
141 patients enrolled in the neratinib monotherapy arm of the trial,
including 124 patients with HER2 mutations and 17 patients with HER3
mutations. This included patients with 21 unique tumor types, with the
most common being breast, lung, bladder and colorectal cancer.
Researchers observed 30 distinct HER2 and 12 distinct HER3 mutations
among these patients, with the most frequent HER2 variants involving
amino acids S310, L755, A755_G776insYVMA and V777.
In the HER2-mutant cohort, clinical responses were observed in tumors
with S310, L755, V777, P780_Y781insGSP and A775_G776insYVMA mutations.
When stratified by tumor type, responses were observed in patients with
breast, cervical, biliary, salivary and non-small-cell lung cancers,
which led to cohort expansions in these tumor types. No activity was
observed in the HER3-mutant cohort.
The neratinib safety profile observed in the SUMMIT study is consistent
with that observed previously in metastatic patients with HER2 amplified
tumors. The study showed that the most frequently observed adverse
reaction was diarrhea. All patients in the SUMMIT study received
prophylactic loperamide (16 mg per day initially) for the first cycle of
treatment in order to reduce neratinib-related diarrhea, and with this
anti-diarrheal prophylaxis and management, diarrhea was not a
treatment-limiting side effect in SUMMIT. For the 141 patients enrolled
in the neratinib monotherapy arm with safety data available, 31 patients
(22.0%) reported grade 3 diarrhea. The median duration of grade 3
diarrhea for those patients was two days. Four patients (2.8%)
permanently discontinued neratinib and 21 patients (14.9%) had dose
interruptions due to diarrhea.
“Results to date from the SUMMIT trial validate the ‘next-generation’
basket trial approach, which has enabled us to efficiently and
effectively evaluate neratinib across numerous cancer types as well as
individual and sometimes entirely novel HER2 mutations,” said David
Hyman, M.D., Chief of the Early Drug Development Service at Memorial
Sloan Kettering Cancer Center (MSK). “We look forward to completing
enrollment in the ongoing cohorts in the study and continuing to utilize
the basket trial design to explore the most optimal treatment options
for these select patient populations.”
Dr. Hyman, who helped pioneer the concept of basket trials at MSK,
presented the initial findings from the SUMMIT study at the American
Association for Cancer Research Annual Meeting in April 2017.
“We are very pleased with these initial results,” said Mr. Auerbach. “We
look forward to advancing neratinib into further clinical development in
multiple HER2 mutant tumor types, both as monotherapy and in novel
combinations.”
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, oral was
approved by the U.S. Food and Drug Administration in July 2017 for the
extended adjuvant treatment of adult patients with early stage
HER2-overexpressed/amplified breast cancer, following adjuvant
trastuzumab-based therapy, and is marketed in the United States as
NERLYNX® (neratinib) tablets. NERLYNX is a registered
trademark of Puma Biotechnology, Inc.
Important Safety Information (ISI)
NERLYNX
®
(neratinib) tablets, for oral use
INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated
for the extended adjuvant treatment of adult patients with early-stage
HER2 overexpressed/amplified breast cancer, to follow adjuvant
trastuzumab-based therapy.
CONTRAINDICATIONS: None
WARNINGS AND PRECAUTIONS:
-
Diarrhea: Aggressively manage diarrhea occurring despite
recommended prophylaxis with additional antidiarrheals, fluids, and
electrolytes as clinically indicated. Withhold NERLYNX in patients
experiencing severe and/or persistent diarrhea. Permanently
discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade
≥ 2 diarrhea that occurs after maximal dose reduction.
-
Hepatotoxicity: Monitor liver function tests monthly for the
first 3 months of treatment, then every 3 months while on treatment
and as clinically indicated. Withhold NERLYNX in patients experiencing
Grade 3 liver abnormalities and permanently discontinue NERLYNX in
patients experiencing Grade 4 liver abnormalities.
-
Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise
patients of potential risk to a fetus and to use effective
contraception.
ADVERSE REACTIONS: The most common adverse reactions (≥ 5%) were
diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis,
decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail
disorder, dry skin, abdominal distention, epistaxis, weight decreased
and urinary tract infection.
To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology,
Inc. at 1-844-NERLYNX (1-844-637-5969) and
www.NERLYNX.com
or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch
.
DRUG INTERACTIONS:
-
Gastric acid reducing agents: Avoid concomitant use with proton pump
inhibitors (PPI) and H2-receptor antagonists. Separate NERLYNX by 3
hours after antacid dosing.
-
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
-
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
-
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of
narrow therapeutic agents that are P-gp substrates when used
concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:
-
Lactation: Advise women not to breastfeed.
Please see
Full
Prescribing Information
for additional safety information.
The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given
orally once daily with food, continuously for one year. Antidiarrheal
prophylaxis should be initiated with the first dose of NERLYNX and
continued during the first 2 months (56 days) of treatment and as needed
thereafter.
To help ensure patients have access to NERLYNX, Puma has implemented the
Puma Patient Lynx support program to assist patients and healthcare
providers with reimbursement support and referrals to resources that can
help with financial assistance. More information on the Puma Patient
Lynx program can be found at www.NERLYNX.com
or 1-855-816-5421.
Further information about Puma Biotechnology can 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 fact
that the Company has only recently commenced commercialization and
shipment of its only FDA approved product; the Company’s dependence upon
the commercial success of NERLYNX (neratinib); the Company’s history of
operating losses and its expectation that it will continue to incur
losses for the foreseeable future; risks and uncertainties related to
the Company’s ability to achieve or sustain profitability; the Company’s
ability to predict its future prospects and forecast its financial
performance and growth; failure to obtain sufficient capital to fund the
Company’s operations; the effectiveness of sales and marketing efforts;
the Company’s ability to obtain FDA approval or other regulatory
approvals in the United States or elsewhere for other indications for
neratinib or other product candidates; 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; risks pertaining to securities class action, derivative and
defamation lawsuits; 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 Quarterly Report
on Form 10-Q for the quarter ended September 30, 2017. 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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