ARIAD Presents Updated Phase 1 Data on AP26113 in Patients with Non-Small
Cell Lung Cancer
~ Phase 2 Trial of AP26113 Now Enrolling Patients
~Investor Meeting and Webcast on Monday, June 3 at 7:30 a.m. CT
2013 ASCO Annual Meeting
CHICAGO & CAMBRIDGE, Mass. -- June 2, 2013
ARIAD 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. The study confirms compelling clinical evidence of the
anti-tumor activity of AP26113 at multiple dose levels in patients with
anaplastic lymphoma kinase positive (ALK+) NSCLC, including brain metastases,
and initial clinical evidence of anti-tumor activity in patients with
epidermal growth factor receptor mutant (EGFRm) NSCLC.
The study identified a recommended Phase 2 dose of 180 mg administered orally
once daily. The Phase 2 portion of the trial is now open and enrolling
patients at this dose in the first four expansion cohorts. Further Phase 1
evaluation of the 240 mg dose is continuing in NSCLC patients with documented
EGFRm and the secondary mutation, T790M, following disease progression on
prior EGFR TKI therapy.
The Phase 1 results are being presented this morning at the 2013 American
Society of Clinical Oncology (ASCO) Annual Meeting being held in Chicago.
Phase 1 Study Design
Patients enrolled in the Phase 1 portion of the trial had advanced solid
tumors that were refractory to available therapies or had no standard or
curative treatment available. The objectives of the Phase 1 portion of the
trial were to determine the recommended dose for further study of AP26113 and
to characterize its safety (including the maximum tolerated dose, MTD),
pharmacokinetics, and preliminary anti-tumor activity. The trial used an
open-label, dose-escalating design. Anti-tumor activity was determined by
serial CT scans using RECIST criteria.
Fifty-five patients were enrolled in the study at seven dose levels (i.e., 30,
60, 90, 120, 180, 240 and 300 mg per day, administered orally). Six patients
received twice-a-day (BID) dosing. Twenty-two patients currently remain on
Forty-seven of the patients enrolled in the study to date have NSCLC,
including 24 who are ALK+ and 19 who are EGFRm. Two-thirds of these patients
failed three or more regimens of prior systemic anti-tumor treatment,
including both targeted therapies and chemotherapy.
“Results from this ongoing trial confirm that AP26113 has promising anti-tumor
activity in patients with ALK+ NSCLC and other ALK+ tumors, including brain
metastases in these patients,” stated D. Ross Camidge, M.D., Ph.D. Associate
Professor of Medicine at University of Colorado School of Medicine, the
study’s presenter at ASCO. “Additionally, initial objective evidence of
anti-tumor activity has been demonstrated in a patient with EGFR-mutant lung
Key data from the study presented at ASCO include:
Safety and Tolerability
*Safety assessments show AP26113 to be well tolerated. The most common
adverse events (AEs), regardless of treatment relationship and including
all grades, were fatigue (40%) and nausea (36%). The only
treatment-related AEs that occurred in at least 10% of study patients were
nausea (33%), fatigue (22%), and diarrhea (20%).
*Serious AEs (regardless of treatment relationship) were uncommon. Events
occurring in two or more patients were: pneumonia (7%), cough (4%),
dyspnea (4%), hypoxia (4%), and pleural effusion (4%). No signs of rash
that would be considered typical of EGFR inhibitors were seen at any doses
*There were two patients with a reported dose-limiting toxicity (DLT). One
patient experienced elevated alanine aminotransferase (ALT), a liver
enzyme, at 240 mg per day; the event resolved, and the patient remains on
study. A separate patient experienced dyspnea (shortness of breath) and
hypoxia (reduction of oxygen supply) at 300 mg per day. This patient
discontinued from the study.
*Additionally, isolated events of dyspnea and hypoxia were observed during
initial dose-cohort expansions at 120 mg and 180 mg per day. In one case
at 180 mg per day, the event occurred after one dose of AP26113 in a
patient who subsequently died. The cause of death was adenocarcinoma of
the lung, extremely widely metastatic to both lungs; the investigator
thought AP26113 may have been a contributory factor. As a result, lower
dose cohorts (90 mg, 120 mg, and 180 mg, including BID dosing) were
expanded using modified eligibility criteria, and no further AEs of this
nature were observed in any of the more recently enrolled patients (N =
*Objective responses were observed in ALK+ NSCLC patients at the lowest
dose tested (60 mg), and responses were observed in patients who were
either naïve or resistant to crizotinib (Xalkori^®) – the currently
available first-generation ALK inhibitor.
*Of the 24 ALK+ patients evaluable for response, 15 (63%) demonstrated an
objective response, including 14 partial responses (PR) and one complete
response (CR). Of the 16 crizotinib-resistant NSCLC patients, 12 (75%)
treated with AP26113 demonstrated a PR. Of the two crizotinib-naïve NSCLC
patients, one treated with AP26113 demonstrated a CR. Objective-response
durations ranged from 3 months to 9 months, with responses in 10 of the 15
patients (67%) ongoing. The “waterfall plot” analysis demonstrated tumor
shrinkage in nearly all ALK+ patients.
*Of particular note, four out of five ALK+ patients had a response in
pre-existing brain metastases, and all four remain on study, with the
longest duration of 6 months. This includes one ALK+ patient who was
crizotinib-resistant and also resistant to the investigational agent
*Of the 20 patients who had a history of EGFRm, 18 were evaluable for
response. Ten EGFRm patients had a history of a T790M secondary mutation
during or after prior erlotinib (Tarceva^®) therapy and had also failed
rounds of chemotherapy, targeted therapy, and/or other investigational
*Of the 18 evaluable patients, one EGFRm patient (EGFR exon-19 deletion by
history, T790M status unknown) achieved a PR and remains on study
(duration, 6 months), and seven patients had stable disease (SD).
*Of the 10 patients with a history of a T790M secondary mutation, four
patients had SD on AP26113, with durations ranging from 2 months to 9
months, and one SD is ongoing (duration, 4 months).
*Three of the 10 T790M patients had their T790M status documented during or
after their most recent EGFR TKI, and had EGFR TKI as their last therapy
prior to receiving AP26113 (with an intervening period of more than one
month). Two of these patients had SD on AP26113, and the third
discontinued prior to receiving a follow-up scan.
Pharmacokinetics and Dose Selection
*Pharmacokinetic data indicate that the median plasma levels at doses of
180 mg and 240 mg once daily remain above the IC50 values determined
pre-clinically for inhibition of ALK, c-ros oncogene-1 (ROS1) and EGFRm,
and their secondary resistance mutations, for the entire 24 hour dosing
*The MTD has not been identified. Based on safety, efficacy, and
pharmacokinetic data, the recommended Phase 2 dose for ALK+, ROS1+ and
EGFRm patients is 180 mg once daily. This dose will be used in the Phase 2
portion of the ongoing Phase 1/2 trial and in the pivotal trial of AP26113
in patients who are ALK+ NSCLC patients who are crizotinib-resistant.
*In parallel, further Phase 1 testing at the 240 mg dose level is underway
in patients with documented EGFRm T790M secondary mutation, following
disease progression on prior EGFR TKI therapy, potentially supporting
further dose escalation in individual patients.
Phase 2 Portion of Trial Now Enrolling Patients
The Phase 2 portion of the ongoing Phase 1/2 clinical trial is now enrolling
patients at nine sites in the United States and Europe. The Phase 2 portion of
the trial consists of five expansion cohorts: (1) ALK+ treatment naïve NSCLC,
(2) ALK+ resistant to crizotinib NSCLC, (3) EGFRm resistant to one prior EGFR
TKI with documented T790M NSCLC, (4) ROS1+ NSCLC and other targets, and (5)
ALK+, either naïve or resistant to crizotinib, NSCLC with active brain
metastases. This fifth expansion cohort will begin enrolling patients in the
third quarter of 2013.
Cohort 3 in the Phase 2 portion of the ongoing study is enrolling patients
with T790M-mediated resistance to one prior EGFR TKI. Patients will have a
documented T790M secondary mutation of EGFR following disease progression on
the most recent course of EGFR TKI therapy, and will have stopped that therapy
within 30 days prior to initiating AP26113. No intervening therapy prior to
starting AP26113 will be permitted.
“We believe AP26113 will be a compelling new medicine for patients with
ALK-positive lung cancer and look forward to evaluating AP26113 in a
rigorously defined EGFRm patient population with T790M-mediated resistance in
the Phase 2 portion of the ongoing clinical trial,” stated Frank G. Haluska,
M.D., Ph.D., senior vice president of clinical research and development and
chief medical officer at ARIAD. “In parallel to enrollment in the Phase 2
expansion cohorts, we plan to begin a pivotal trial of AP26113 in ALK-positive
NSCLC patients who are resistant to crizotinib in the third quarter of 2013.”
Investor and Analyst Briefing and Webcast
A breakfast meeting to review the most recent clinical data from the Phase 1
portion of the ongoing Phase 1/2 clinical trial of AP26113 with research
analysts and institutional investors will feature Scott Gettinger, M.D.,
Associate Professor of Medicine at Yale School of Medicine and members of
ARIAD’s management. This meeting will be webcast live along with presentation
slides and can be accessed by visiting the investor relations section of the
Company’s website at http://investor.ariad.com.
A replay of this investor event will be available on the ARIAD website
approximately three hours after the presentation and will be archived for
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.comor follow ARIAD on
Xalkori^® is a registered trademark of Pfizer, Inc. Tarceva^® is a registered
trademark of Astellas Pharma US, Inc.
This press release contains “forward-looking statements” including, but not
limited to, statements relating to preclinical and 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 detailed 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.
ARIAD Pharmaceuticals, Inc.
Kendra Adams, 617-503-7028
Liza Heapes, 617-621-2315
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