ARIAD Presents Updated Phase 1/2 Clinical Data on Brigatinib in Patients with ALK+ Non-Small Cell Lung Cancer
April 15 2016 - 07:35AM
Business Wire
ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced
updated clinical data on its investigational tyrosine kinase
inhibitor, brigatinib, in patients with advanced malignancies,
including anaplastic lymphoma kinase positive (ALK+) non-small cell
lung cancer (NSCLC), from an ongoing Phase 1/2 trial. This report
includes updated data on the brigatinib safety profile and
pharmacokinetics (PK) from all patients treated in the trial, with
a focus on brigatinib clinical activity in patients with ALK+
NSCLC, including those with intracranial CNS metastases at study
entry. The report also details overall survival outcomes of
patients in the study.
The updated results were presented at the 6th European Lung
Cancer Conference (ELCC) being held in Geneva, Switzerland.
Phase 1/2 Study
The data presented at ELCC include pharmacokinetics and safety
analyses on all patients in the trial (n=137) and efficacy analyses
on patients with ALK+ NSCLC (n=79). The presentation is based on
patient data as of February 2015 with a median time on treatment
for ALK+ NSCLC patients of 12.6 months (range, 0.03 – 35.5+
months). Patient enrollment in the trial is complete, with the last
patient enrolled in July 2014. The primary endpoint in the Phase 2
portion of the trial is overall response rate. Secondary endpoints
include safety and tolerability, pharmacokinetic parameters,
progression free survival, and overall survival.
“The updated data from the Phase 1/2 trial of brigatinib show a
one year overall survival rate of 100 percent in crizotinib-naive
patients, and 81 percent in patients with prior crizotinib
treatment,” stated Rafael Rosell, M.D., Director, Cancer Biology
& Precision Medicine Program Catalan Institute of Oncology,
Germans Trias i Pujol Health Sciences Institute and Hospital in
Barcelona, Spain. “In addition, the new data show predictable
pharmacokinetics, with drug exposure increasing proportionally with
dose. The Phase 1/2 trial has provided important long-term
follow-up data on the safety and efficacy of this promising drug
candidate.”
Key Data Update from Study
Anti-tumor Activity – ALK+ NSCLC Patients:
- Of the 70 evaluable ALK+ NSCLC patients
with prior crizotinib therapy treated with brigatinib, median
progression-free survival (PFS) was 13.4 months. Median PFS was not
yet reached in ALK+ NSCLC patients who were crizotinib-naive
(n=8).
- The “waterfall plot” analysis
demonstrated tumor shrinkage in nearly all evaluable ALK+ NSCLC
patients, with 25 patients experiencing 100% shrinkage of the
target lesion.
- Of the eight evaluable TKI-naive ALK+
NSCLC patients treated with brigatinib, all demonstrated an
objective response (100%), including three complete responses.
Seven responses were confirmed.
- Of the 70 evaluable ALK+ NSCLC patients
with prior crizotinib therapy treated with brigatinib, 50 (71%)
demonstrated an objective response, including four complete
responses. Forty-three responses were confirmed.
- The one-year overall survival (OS) rate
in ALK+ NSCLC crizotinib-naive patients (n=8) was 100 percent and
the projected two-year OS is also estimated to be 100 percent. Of
the 71 ALK+ NSCLC patients who received prior treatment with
crizotinib, the one-year OS was estimated to be 81 percent with
projected two-year OS estimated to be 71 percent.
- An evaluation of the efficacy of
brigatinib in ALK+ NSCLC patients with intracranial CNS metastases
at baseline was also included in the ELCC presentation. In an
independent central review of brain magnetic resonance imaging
(MRI) scans, 50 of 79 ALK+ NSCLC patients were identified to have
intracranial CNS metastases at baseline.
- Of these 50 patients, 17 had measurable
intracranial CNS metastases (15 evaluable), and 33 patients had
only non-measurable intracranial CNS metastases (31
evaluable).
- 8 of 15 (53%) patients with measurable
intracranial CNS metastases had at least 30% reduction in
intracranial target lesion diameter, and 11 of 33 (33%) with only
non-measurable intracranial CNS metastases had complete
disappearance of intracranial lesions.
- Median intracranial PFS for evaluable
ALK+ NSCLC patients with intracranial CNS metastases at baseline
was 15.6 months.
Pharmacokinetics:
- The brigatinib plasma steady-state
parameters increased proportionally with dose over the dose range
of 60 to 240 mg once daily.
- The geometric mean average plasma
concentrations of brigatinib at steady state at 90 mg once daily
and 180 mg once daily exceed the IC50 values for native ALK and all
clinically relevant ALK resistance mutants tested.
Safety and Tolerability – All Patients Enrolled:
- The most common treatment-emergent
adverse events (TEAEs; ≥ 30%), regardless of treatment
relationship, were nausea (52%), fatigue (42%), diarrhea (40%),
headache (33%), and cough (32%).
- TEAEs, grade 3 or higher, occurring in
three or more patients were increased lipase (9%), dyspnea (7%),
hypertension (5%), hypoxia (5%), neoplasm progression (5%),
pneumonia (5%), increased amylase (4%), fatigue (4%), and pulmonary
embolism (≥3%).
- Serious AEs, all causality, occurring
in three or more patients were dyspnea (7%), pneumonia (6%),
hypoxia (5%), neoplasm progression (5%), pulmonary embolism (3%),
malignant pericardial effusion (2%), and pyrexia (2%).
- A subset of pulmonary events, including
dyspnea, hypoxia, pneumonia and/or pneumonitis, often with
radiographic findings of linear or ground-glass pulmonary
opacities, were observed in 8% (11/137) of patients within 7 days
of dosing. The incidence of these early-onset pulmonary events was
lower with a starting dose of 90 mg (1/50 patients, 2%) vs. 180 mg
(6/44 patients, 14%). In addition, no early-onset pulmonary events
were observed after dose escalation in the 32 patients started at
90 mg and escalated to 180 mg after seven days.
“As we continue to study brigatinib in the ongoing Phase 1/2
trial, the pivotal Phase 2 ALTA trial and the new Phase 3 ALTA 1L
trial in the front-line setting, we are encouraged by the potential
of this targeted drug candidate for patients with ALK positive
NSCLC and are looking forward to an NDA submission later this
year,” stated Timothy P. Clackson, Ph.D., president of research and
development and chief scientific officer at ARIAD. “The safety, PK
and efficacy results reported with this update provide the
potential for differentiation of brigatinib in the
crizotinib-resistant patient population.”
About ARIADARIAD Pharmaceuticals, Inc., headquartered in
Cambridge, Massachusetts and Lausanne, Switzerland, is an orphan
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 orphan
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).
Forward-Looking StatementsThis press release contains
forward-looking statements, each of which are qualified in their
entirety by this cautionary statement. Any statements contained
herein which do not describe historical facts, including, but not
limited to, the statements made by Dr. Clackson, are
forward-looking statements that 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 factors, risks and uncertainties
include, but are not limited to, our ongoing strategic review, our
ability to successfully commercialize and generate profits from
sales of Iclusig and our product candidates, if approved;
competition from alternative therapies; our ability to meet
anticipated clinical trial commencement, enrollment and completion
dates and regulatory filing dates for our products and product
candidates and to move new development candidates into the clinic;
our ability to execute on our key corporate initiatives; regulatory
developments and safety issues, including difficulties or delays in
obtaining regulatory and pricing and reimbursement approvals to
market our products; our reliance on the performance of third-party
manufacturers and specialty pharmacies for the supply and
distribution of our products and product candidates; the occurrence
of adverse safety events with our products and product candidates;
the costs associated with our research, development, manufacturing,
commercialization and other activities; the conduct, timing and
results of preclinical and clinical studies of our products and
product candidates, including that preclinical data and early-stage
clinical data may not be replicated in later-stage clinical
studies; the adequacy of our capital resources and the availability
of additional funding; the ability to satisfy our contractual
obligations, including under our leases, convertible debt and
royalty financing agreements; patent protection and third-party
intellectual property claims; litigation; our operations in foreign
countries; risks related to key employees, markets, economic
conditions, health care reform, prices and reimbursement rates; and
other risk factors detailed in our public filings with the U.S.
Securities and Exchange Commission, including our most recent
Annual Report on Form 10-K and subsequent Quarterly Reports on Form
10-Q. Except as otherwise noted, these forward-looking statements
speak only as of the date of this press release and we undertake no
obligation to update or revise any of these statements to reflect
events or circumstances occurring after this press release. We
caution investors not to place considerable reliance on the
forward-looking statements contained in this press release.
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ARIAD Pharmaceuticals, Inc.For InvestorsMaria Cantor,
617-621-2208Maria.cantor@ariad.comorFor MediaLiza Heapes,
617-620-4888Liza.heapes@ariad.com
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