Pfizer Inc. (NYSE:PFE) and Merck & Co. Inc. (NYSE:MRK), known as MSD
outside the United States and Canada, through a subsidiary, announced
today that they have entered into an agreement to explore the
therapeutic potential of the combination of Pfizer’s crizotinib (XALKORI®)
with Merck’s investigational anti-PD-1 antibody pembrolizumab, in a
Phase 1b clinical study evaluating the safety and tolerability of the
combination in patients with ALK-positive advanced or metastatic
non-small cell lung cancer (NSCLC). The financial terms of the agreement
were not disclosed.
“This collaboration between Pfizer and Merck is just one example of the
willingness of sponsors to work together in an effort to accelerate
progress against some of the most difficult-to-treat cancers,” said Dr.
Mace Rothenberg, senior vice president of Clinical Development and
Medical Affairs and chief medical officer for Pfizer Oncology.
“Understanding the effects of combining one drug, XALKORI, which
inhibits an abnormally activated enzyme in patients with ALK-positive
metastatic lung cancer, with the investigational drug, pembrolizumab,
which harnesses the body’s immune system to fight cancer, is vital if we
are to continue to advance the care of lung cancer patients.”
This multi-center, open-label clinical study is expected to begin in
2015. Pfizer will conduct the study.
“We are pleased to build upon our ongoing collaboration with Pfizer to
evaluate potential combination regimens incorporating Merck’s
investigational immunotherapy pembrolizumab,” said Dr. Eric Rubin, vice
president, Oncology, Merck Research Laboratories. “Evidence from early
studies of pembrolizumab monotherapy together with XALKORI’s proven
targeted therapeutic approach provides the scientific rationale for
evaluating this combination for the treatment of lung cancer.”
Both companies previously announced plans to evaluate the safety and
efficacy of pembrolizumab in combination with Pfizer’s small molecule
kinase inhibitor axitinib (INLYTA®) in patients with renal
cell carcinoma. Separately, pembrolizumab plus Pfizer’s PF-05082566
(PF-2566), an investigational immuno-oncology agent that targets the
human 4-1BB receptor, will be evaluated in multiple cancer types. These
studies are expected to begin enrollment later this year.
About Pembrolizumab
Pembrolizumab (MK-3475) is an investigational, humanized, monoclonal
antibody against PD-1 designed to reactivate anti-tumor immunity.
Pembrolizumab exerts dual ligand blockade of the PD-1 pathway by
inhibiting the interaction of PD-1 on T cells with its ligands PD-L1 and
PD-L2.
Pembrolizumab is currently being evaluated across more than 30 types of
cancers, as monotherapy and in combination. It is anticipated that by
the end of 2014, the pembrolizumab development program will grow to more
than 24 clinical trials, enrolling an estimated 6,000 patients at nearly
300 clinical trial sites worldwide. For information about Merck’s
oncology clinical studies, please visit http://www.merck.com/clinical-trials/index.html.
XALKORI® (crizotinib) Indication and
Important Safety Information
XALKORI is a kinase inhibitor indicated for the treatment of patients
with metastatic non-small cell lung cancer (NSCLC) whose tumors are
anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved
test.
Hepatotoxicity: Across three main clinical trials fatal hepatotoxicity
occurred in 0.2% of patients. Monitor with periodic liver testing.
Temporarily suspend, dose reduce, or permanently discontinue XALKORI.
Pneumonitis: Across three main clinical trials interstitial lung disease
(ILD)/pneumonitis occurred in 2% of patients. Permanently discontinue in
patients with ILD/pneumonitis.
QT Interval Prolongation: Across three main clinical trials QT interval
prolongation occurred in 2.7% of patients. Monitor with
electrocardiograms and electrolytes in patients who have a history of or
predisposition for QTc prolongation, or who are taking medications that
prolong QT. Temporarily suspend, dose reduce, or permanently discontinue
XALKORI.
Bradycardia: Xalkori can cause bradycardia. Across three main clinical
trials 11% of patients experienced a heart rate of less than 50 beats
per minute. Monitor heart rate and blood pressure regularly. Temporarily
suspend, dose reduce, or permanently discontinue XALKORI.
Embryofetal Toxicity: XALKORI can cause fetal harm when administered to
a pregnant woman. Women of childbearing potential should be advised to
avoid becoming pregnant while receiving XALKORI.
Adverse Reactions: Across three main clinical trials the most common
adverse reactions (≥25%) were vision disorders, nausea, diarrhea,
vomiting, constipation, edema, elevated transaminases, and fatigue.
In a phase 3 study in patients with ALK-positive metastatic NSCLC
randomized to XALKORI (n=172) or chemotherapy (n=171), serious adverse
reactions were reported in 37.2% of patients treated with XALKORI. The
most frequent serious adverse reactions reported in patients treated
with XALKORI were pneumonia (4.1%), pulmonary embolism (3.5%), dyspnea
(2.3%), and ILD (2.9%). Fatal adverse reactions in XALKORI-treated
patients occurred in 9 (5%) patients, consisting of: acute respiratory
distress syndrome, arrhythmia, dyspnea, ILD, pneumonia, pneumonitis,
pulmonary embolism, respiratory failure, and sepsis. Grade 3 or 4 events
occurring at a higher incidence with XALKORI than with chemotherapy and
at greater than 2%, were syncope (3%), QT prolongation (3%), and
pulmonary embolism (5%). Elevation of ALT of any grade occurred in 76%
of patients and grade 3 or 4 in 17% of patients. Neutropenia of any
grade occurred in 49% of patients and grade 3 or 4 in 12% of patients.
Lymphopenia of any grade occurred in 51% of patients and grade 3 or 4 in
9% of patients. Renal cysts occurred in 4% and neuropathy occurred in
19% of patients treated with XALKORI.
Drug Interactions: Exercise caution with concomitant use of moderate
CYP3A inhibitors. Avoid grapefruit or grapefruit juice which may
increase plasma concentrations of crizotinib. Avoid concomitant use of
strong CYP3A inducers and inhibitors. Dose reduction may be needed for
co-administered drugs that are predominantly metabolized by CYP3A.
Nursing Mothers: Given the potential for serious adverse reactions in
nursing infants, consider whether to discontinue nursing or discontinue
XALKORI.
Hepatic Impairment: XALKORI has not been studied in patients with
hepatic impairment. As crizotinib is extensively metabolized in the
liver, hepatic impairment is likely to increase plasma crizotinib
concentrations. Use caution in patients with hepatic impairment.
Renal Impairment: Administer XALKORI at a starting dose of 250 mg taken
orally once daily in patients with severe renal impairment (CLcr<30
mL/min) not requiring dialysis. No starting dose adjustment is needed
for patients with mild and moderate renal impairment.
For more information and full prescribing information, please visit www.XALKORI.com.
About Pfizer Oncology
Pfizer Oncology is committed to the discovery, investigation and
development of innovative treatment options to improve the outlook for
cancer patients worldwide. Our strong pipeline of biologics and small
molecules, one of the most robust in the industry, is studied with
precise focus on identifying and translating the best scientific
breakthroughs into clinical application for patients across a wide range
of cancers. By working collaboratively with academic institutions,
individual researchers, cooperative research groups, governments, and
licensing partners, Pfizer Oncology strives to cure or control cancer
with breakthrough medicines, to deliver the right drug for each patient
at the right time. For more information, please visit www.Pfizer.com.
About Merck Oncology
At Merck Oncology, our goal is to translate breakthrough science into
biomedical innovations to help people with cancer worldwide. Harnessing
immune mechanisms to fight cancer is the priority focus of our oncology
research and development program. The Company is advancing a pipeline of
immunotherapy candidates and combination regimens. Cancer is one of the
world's most urgent unmet medical needs. Helping to empower people to
fight cancer is our passion. For information about Merck’s commitment to
Oncology visit the Oncology Information Center at http://www.mercknewsroom.com/oncology-infocenter.
About Merck
Today's Merck is a global healthcare leader working to help the world be
well. Merck is known as MSD outside the United States and Canada.
Through our prescription medicines, vaccines, biologic therapies, and
consumer care and animal health products, we work with customers and
operate in more than 140 countries to deliver innovative health
solutions. We also demonstrate our commitment to increasing access to
healthcare through far-reaching policies, programs and partnerships. For
more information, visit www.merck.com and
connect with us on Twitter, Facebook
and YouTube.
PFIZER DISCLOSURE NOTICE
The information contained in this release is as of August 26, 2014.
Pfizer assumes no obligation to update forward-looking statements
contained in this release as the result of new information or future
events or developments.
This release contains forward-looking information about an agreement
between Pfizer and Merck to study the anti-cancer therapeutic potential
of Pfizer’s XALKORI in combination with Merck’s investigational
anti-PD-1 antibody pembrolizumab (MK-3475), as well as agreements
entered into earlier this year between Pfizer and Merck to study the
anti-cancer therapeutic potential of Pfizer’s INLYTA (axitinib) and
PF-2566 in combination with Merck’s pembrolizumab, that involves
substantial risks and uncertainties that could cause actual results to
differ materially from those expressed or implied by such statements.
Risks and uncertainties include, among other things, the
uncertainties inherent in research and development, including the
ability to meet anticipated clinical study commencement and completion
dates as well as the possibility of unfavorable study results; whether
and when drug applications may be filed in any jurisdictions for any of
the combination therapies; whether and when any such applications may be
approved by regulatory authorities, as well as their decisions regarding
labeling and other matters that could affect the availability or
commercial potential of any of the combination therapies; and
competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2013 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information That May Affect Future Results”, as well as in its
subsequent reports on Form 8-K, all of which are filed with the SEC and
available at www.sec.gov and
www.pfizer.com.
Merck Forward-Looking Statement
This news release includes “forward-looking statements” within the
meaning of the safe harbor provisions of the United States Private
Securities Litigation Reform Act of 1995. These statements are based
upon the current beliefs and expectations of Merck’s management and are
subject to significant risks and uncertainties. There can be no
guarantees with respect to pipeline products that the products will
receive the necessary regulatory approvals or that they will prove to be
commercially successful. If underlying assumptions prove inaccurate or
risks or uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements.
Risks and uncertainties include, but are not limited to, general
industry conditions and competition; general economic factors, including
interest rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and healthcare legislation in the
United States and internationally; global trends toward healthcare cost
containment; technological advances, new products and patents attained
by competitors; challenges inherent in new product development,
including obtaining regulatory approval; Merck’s ability to accurately
predict future market conditions; manufacturing difficulties or delays;
financial instability of international economies and sovereign risk;
dependence on the effectiveness of Merck’s patents and other protections
for innovative products; and the exposure to litigation, including
patent litigation, and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking
statement, whether as a result of new information, future events or
otherwise. Additional factors that could cause results to differ
materially from those described in the forward-looking statements can be
found in Merck’s 2013 Annual Report on Form 10-K and the company’s other
filings with the Securities and Exchange Commission (SEC) available at
the SEC’s Internet site (www.sec.gov).
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