|[May 31, 2014]
ARIAD Presents Updated Phase 1/2 Data on AP26113 in Patients with ALK+ Non-Small Cell Lung Cancer
CHICAGO & CAMBRIDGE, Mass. --(Business Wire)--
Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced updated
clinical results on its investigational tyrosine kinase inhibitor (TKI), AP26113,
in patients with advanced non-small cell lung cancer (NSCLC) from an
ongoing Phase 1/2 trial. These study results show anti-tumor activity of
AP26113 in patients with crizotinib-resistant anaplastic lymphoma kinase
(ALK) positive NSCLC, including patients with brain metastases.
Crizotinib is approved for ALK-positive NSCLC patients.
The updated Phase 1/2 results are being presented this afternoon at the
2014 American Society of Clinical Oncology (ASCO) annual meeting in
Phase 1/2 Study Design
The objectives of the Phase 1 portion of the trial were to characterize
the safety and tolerability of AP26113, pharmacokinetics, and
preliminary anti-tumor activity and to determine the recommended dose
for further study of AP26113 in subsequent clinical trials. The trial
used an open-label, dose-escalating design. The study initially
identified a recommended Phase 2 dose of 180 mg administered orally once
A total of 125 patients have been enrolled in the ongoing Phase 1/2
trial. The Phase 2 portion of the trial enrolled 59 patients and began
in June 2013 in the United States and Europe. This portion of the trial
consists of five expansion cohorts. The data presented at ASCO focus on
the 71 patients with a history of ALK+ tumors in the entire trial.
Fifty-three of these patients currently remain on study.
"The data from the Phase 2 portion of the trial show that AP26113
exhibits anti-tumor activity in patients with crizotinib-resistant ALK
rearranged NSCLC, as well as crizotinib-naïve ALK rearranged NSCLC,"
stated Scott N. Gettinger, M.D., associate professor of medicine at Yale
School of Medicine. "Importantly, AP26113 demonstrates activity against
brain metastases in patients with prior crizotinib therapy, including
responses of clinically meaningful duration."
Key data from the study include:
Safety and Tolerability - All Patients Enrolled
The most common adverse events (AEs), regardless of treatment
relationship and including all grades, were nausea (40%), fatigue
(34%), and diarrhea (34%).
Adverse events, grade 3 or higher, were uncommon. Treatment-related
events occurring in three or more patients were dyspnea (4%), hypoxia
(4%), and fatigue (2%).
Serious AEs, all causality, occurring in three or more patients were
dyspnea (7%), hypoxia (4%), pneumonia (4%), neoplasm progression (2%),
and pulmonary embolism (2%).
Early onset pulmonary symptoms were observed in 12 of 125 (10%)
patients enrolled in the study and occurred more frequently at doses
of 180 mg per day and higher compared to the lower doses of 90 mg or
120 mg per day. These early-onset pulmonary symptoms included dyspnea,
hypoxia, and new pulmonary opacities on chest computed tomography
suggestive of pneumonia or pneumonitis. These symptoms occurred within
7 days of initiation of AP26113 and required medical intervention.
To minimize the early-onset pulmonary symptoms observed, two
additional dosing regimens were examined in the phase 2 portion of the
trial: 90 mg per day for 1 week followed by 180 mg per day (n=28) and
90 mg per day continuously (n=10). The incidence of early onset
pulmonary symptoms in these two dosing regimens was 0 of 28 and 1 of
10 patients, respectively. Overall, only 1 out of 38 patients (3%) who
began dosing at 90 mg per day had early-onset pulmonary symptoms.
Anti-tumor Activity -- ALK+ NSCLC Patients
Objective responses were observed in ALK+ NSCLC patients at the lowest
dose tested in these patients (60 mg), and responses were observed in
patients who were either TKI-naïve or resistant to crizotinib.
Of the 57 ALK+ NSCLC patients evaluable for response, 41 (72%)
demonstrated an objective response, including 40 partial responses
(PR) and one complete response (CR).
Of the six TKI-naïve ALK+ NSCLC patients treated with AP26113, all
demonstrated an objective response, including one CR.
Of the 51 crizotinib-resistant ALK+ NSCLC patients treated with
AP26113, 35 (69%) demonstrated an objective response, with response
durations ranging from 1.6 to 14.7+ months. Of the 49 patients with
follow-up scans, median progression-free survival is 10.9 months by
Of particular note, 9 of 13 (69%) ALK+ NSCLC patients with
pre-existing brain metastases had evidence of radiographic improvement
in those metastases, and 11 of these patients remain on study. In
addition, improvement in a patient with leptomeningeal metastasis was
A separate, pivotal global Phase 2 trial of AP26113
in patients with locally advanced or metastatic NSCLC who were
previously treated with crizotinib is open and enrolling patients. The
ALTA (ALK in Lung Cancer Trial of AP26113)
trial is designed to determine the safety and efficacy of AP26113 in
refractory ALK+ NSCLC patients. The trial will enroll approximately 220
patients including those with brain metastasis. Patients will be
randomized 1:1 to receive either 90 mg of AP26113 once per day
continuously or a lead-in dose of 90 mg per day for 7 days followed by
180 mg once per day continuously.
"These updated Phase 1/2 data of AP26113 and in particular the data on
the safety of the two dosing regimens inform the design of the ALTA
trial," stated Frank G. Haluska, M.D., Ph.D., senior vice president of
clinical research and development and chief medical officer at ARIAD.
"With continued responses seen in the ongoing Phase 1/2 trial, we
believe AP26113 has the potential to be a compelling new treatment
option for patients with ALK-positive lung cancer."
Investor and Analyst Briefing and Webcast
ARIAD will host an investor and analyst briefing from ASCO on Monday
June 2, 2014. This breakfast meeting will feature Dr. Lyudmila Bazhenova
from UC San Diego Moores Cancer Center to discuss the AP26113 clinical
data being presented at ASCO, Dr. Michael J. Mauro from Memorial Sloan
Kettering Cancer Center to discuss clinical data on ponatinib in CML,
and Dr. Michael C. Heinrich from Oregon Health and Science University to
discuss ponatinib clinical data in GIST.
The meeting will be webcast live along with slides and can be accessed
by visiting the investor relations section of the Company's website at http://investor.ariad.com.
Monday, June 2, 2014
7:30 a.m. to 8:30 a.m. (CT)
Hilton Chicago, Marquette Room
A replay of the investor event will be available on the ARIAD website
approximately three hours after the presentation and will be archived on
the site for four weeks. To ensure a timely connection to the live
webcast, participants should log onto the webcast at least 15 minutes
prior to the scheduled start time.
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts
and Lausanne, Switzerland, is an integrated global oncology company
focused on transforming the lives of cancer patients with breakthrough
medicines. ARIAD is working on new medicines to advance the treatment of
various forms of chronic and acute leukemia, lung cancer and other
difficult-to-treat cancers. ARIAD utilizes computational and structural
approaches to design small-molecule drugs that overcome resistance to
existing cancer medicines. For additional information, visit http://www.ariad.com or
follow ARIAD on Twitter (News - Alert) (@ARIADPharm).
This press release contains "forward-looking statements" including, but
not limited to, statements relating to the updated clinical data for
AP26113. Forward-looking statements are based on management's
expectations and are subject to certain factors, risks and uncertainties
that may cause actual results, outcome of events, timing and performance
to differ materially from those expressed or implied by such statements.
These risks and uncertainties include, but are not limited to,
preclinical data and early-stage clinical data that may not be
replicated in later-stage clinical studies, the costs associated with
our research, development, manufacturing and other activities, the
conduct, timing and results of pre-clinical and clinical studies of our
product candidates, the adequacy of our capital resources and the
availability of additional funding, and other factors in the Company's
public filings with the U.S. Securities and Exchange Commission. The
information contained in this press release is believed to be current as
of the date of original issue. The Company does not intend to update any
of the forward-looking statements after the date of this document to
conform these statements to actual results or to changes in the
Company's expectations, except as required by law.
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