ARIAD Presents Updated Clinical Data on AP26113 in Patients with ALK+ Non-Small Cell Lung Cancer
September 29 2014 - 7:35AM
Business Wire
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. These study
results show sustained anti-tumor activity of AP26113 in patients
with anaplastic lymphoma kinase (ALK) positive NSCLC, including
patients with active brain metastases. The updated Phase 1/2 trial
now contains more mature data of AP26113, including increasing
depth and durability of response in ALK+ NSCLC patients, as well as
additional safety data.
The updated results were presented on Saturday, September 27 at
the 2014 European Cancer Congress (the 39th ESMO, 33rd ESTRO, 18th
ECCO conference) held in Madrid, Spain.
Phase 1/2 Study Design
A total of 137 patients have been enrolled in the ongoing Phase
1/2 trial in the United States and Europe. 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 Phase 2 portion of the trial consists of five expansion
cohorts. The data presented at ESMO focus on the 79 patients with a
history of ALK+ NSCLC tumors in the entire trial. Fifty-six of
these patients currently remain on study treatment.
“The updated data from the ongoing trial continue to demonstrate
the anti-tumor activity of AP26113 in patients with
crizotinib-resistant ALK rearranged NSCLC, as well as TKI-naïve ALK
rearranged NSCLC,” stated Scott N. Gettinger, M.D., associate
professor of medicine at Yale School of Medicine. “One of the
distinguishing features of the data is the evidence for anti-tumor
activity in the brain, a common site of treatment failure.”
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 (45%), diarrhea (37%), and fatigue (37%).
- Adverse events, grade 3 or higher,
occurring in three or more patients were dyspnea (4%), increased
lipase (4%), hypoxia (4%), fatigue (3%), alanine aminotransferase
(ALT) increased (2%) and amylase increased (2%).
- Serious AEs, all causality, occurring
in three or more patients were dyspnea (7%), pneumonia (5%),
hypoxia (4%), neoplasm progression (4%), pyrexia (2%) and pulmonary
embolism (2%).
- Early onset pulmonary symptoms were
observed in 13 of 137 (10%) patients enrolled in the study and
occurred more frequently with starting doses of 180 mg per day and
higher compared to the lower starting doses. These symptoms
occurred within 7 days of treatment initiation, and in some cases,
included dyspnea, hypoxia, and new pulmonary opacities on chest
imaging.
- 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=32) and 90 mg per day continuously (n=18). The
incidence of early-onset pulmonary symptoms in these two dosing
regimens was 0 of 32 and 2 of 18 patients, respectively. Overall, 2
out of 50 patients (4%) who began dosing at 90 mg per day had
early-onset pulmonary symptoms and continued on treatment.
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 72 ALK+ NSCLC patients evaluable
for response, 52 (72%) demonstrated an objective response. The
“waterfall plot” analysis demonstrated tumor shrinkage in nearly
all ALK+ NSCLC patients, with 16 patients experiencing 100%
shrinkage of the target lesion. The median duration of response was
49 weeks, and the median progression-free survival (PFS) was 56
weeks.
- Of the seven evaluable TKI-naïve ALK+
NSCLC patients treated with AP26113, all demonstrated an objective
response, including two complete responses (CR).
- Of the 65 evaluable ALK+ NSCLC patients
with prior crizotinib therapy treated with AP26113, 45 (69%)
demonstrated an objective response. Median progression-free
survival was 47.3 weeks.
- In a subgroup analysis, 10 of 14 (71%)
ALK+ NSCLC patients with active, untreated or progressing, brain
metastases had evidence of radiographic improvement in those
metastases. Four of these patients demonstrated a CR by independent
review. Of the 10 patients who responded, six remain on study, with
treatment durations up to 105 weeks. In addition, improvement in a
patient with leptomeningeal metastasis was observed.
Pivotal Phase 2 Trial Enrolling Patients
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.
“We anticipate full patient enrollment in the ALTA trial in the
third quarter of next year,” stated Frank G. Haluska, M.D., Ph.D.,
senior vice president of clinical research and development and
chief medical officer at ARIAD. “Based on the continued responses
seen in the ongoing Phase 1/2 trial of AP26113, and in particular,
the 100% response rate and durability of response in the TKI-naïve
patients, we are also actively planning a clinical trial to
evaluate the potential of AP26113 in the newly diagnosed ALK+ lung
cancer setting.”
About ARIAD
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
(@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 initiation,
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.
ARIAD Pharmaceuticals, Inc.For InvestorsKendra Adams,
617-503-7028Kendra.adams@ariad.comorFor MediaLiza Heapes,
617-620-4888Liza.heapes@ariad.com
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