ARIAD Presents Updated Clinical Data on Brigatinib in Patients with ALK+ Non-Small Cell Lung Cancer
April 17 2015 - 7:35AM
Business Wire
ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced
updated clinical data on its investigational tyrosine kinase
inhibitor, brigatinib (AP26113), in patients with anaplastic
lymphoma kinase positive (ALK+) advanced non-small cell lung cancer
(NSCLC) from an ongoing Phase 1/2 trial. The new results include an
analysis of safety and efficacy for patients treated at select
doses of brigatinib and an evaluation of intracranial central
nervous system (CNS) antitumor activity.
The updated results were presented at the 2015 European Lung
Cancer Conference (ELCC) being held in Geneva, Switzerland.
Phase 2 Dose Sub-Analysis
The data presented at ELCC focused on the 98 patients treated at
doses of 90 mg/day (n=18), 90 mg/day for 1 week followed by
escalation to 180 mg/day (n=32), and 180 mg/day (n=48) in the Phase
2 portion of the trial. All patients receiving these doses were
evaluated for safety, and patients with ALK+ NSCLC (n=65) were
evaluated for efficacy. The presentation at ELCC is based on
patient data as of January 19, 2015 with a median follow-up of 40
weeks (range, 0.1 – 150+ weeks).
“The updated data on select doses from the Phase 1/2 trial show
robust anti-tumor activity of brigatinib in patients with
crizotinib-resistant ALK+ NSCLC, with responses now approaching one
year,” 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. “Importantly, by starting at the 90 mg dose, we have seen a
reduction of early-onset pulmonary events observed at the higher
starting doses.”
Key data from the study update include:
Safety Summary
- The most common adverse events (AEs) of
any grade, regardless of treatment relationship, were nausea,
diarrhea, and fatigue and were similar in incidence across all
three dose-cohorts, as follows:
- At 90 mg/day (n=18): nausea (44%),
headache (44%), diarrhea (39%), fatigue (39%), cough (39%), and
increased amylase (33%)
- At 90 mg to 180 mg/day (n=32): diarrhea
(44%), nausea (41%), fatigue (38%), headache (28%), cough (28%),
and increased amylase (28%)
- At 180 mg/day (n=48): nausea (63%),
diarrhea (38%), fatigue (31%), headache (31%), cough (25%), and
increased amylase (15%)
- Serious AEs, regardless of treatment
relationship, occurring in 4% or more patients, were dyspnea,
hypoxia, and pneumonia, as follows:
- At 90 mg/day (n=18): dyspnea (1
patient, 6%), hypoxia (2 patients, 11%), and pneumonia (2 patients,
11%)
- At 90 mg to 180 mg/day (n=32): dyspnea
(2 patients, 6%), hypoxia (1 patient, 3%), and pneumonia (1
patient, 3%)
- At 180 mg/day (n=48): dyspnea (2
patients, 4%), hypoxia (2 patients, 4%), and pneumonia (2 patients,
4%)
- As previously observed and reported,
fewer early-onset pulmonary events, including dyspnea, hypoxia, and
new pulmonary opacities, were reported with a starting dose of 90
mg (2/50 patients, 4%) vs. 180 mg (6/44 patients, 14%).
Importantly, no early-onset pulmonary events were observed in the
32 patients started at 90 mg and escalated to 180 mg after 7
days.
Response Summary
- The median time on study for patients
dosed at 90 mg/day was 33.5 weeks (range, 0.7-150+ weeks), 50.3
weeks (range, 0.1-70+ weeks) for the 90 mg to 180 mg/day cohort,
and 31.4 weeks (range, 0.1-135+ weeks) for the 180 mg/day
cohort.
- Brigatinib was active at each of the
three dosing regimens with similar efficacy among the cohorts:
- Objective response rate (ORR) among the
14 evaluable ALK+ NSCLC patients dosed at 90 mg/day was 79% (11
patients, 7 confirmed).
- Among the 26 evaluable ALK+ NSCLC
patients dosed at 90 mg/day for 1 week followed by 180 mg/day, ORR
was 81% (21 patients, 19 confirmed), including 3 patients (12%)
with a complete response (CR).
- Among the 25 evaluable ALK+ NSCLC
patients dosed at 180 mg/day, ORR was 68% (17 patients, 16
confirmed), including 2 patients (8%) with a CR.
- Median duration of response was 11.2
months for the 90 mg/day cohort, not yet reached for the 90 mg to
180 mg/day cohort, and 9.2 months for the 180 mg/day cohort.
- Median progression-free survival (PFS)
was 12.9 months for the 90 mg /day cohort, not yet reached for the
90 mg to 180 mg/day cohort, and 11.1 months for the 180 mg/day
cohort.
Phase 1/2 Analysis of CNS Antitumor Activity
A separate evaluation of the efficacy and safety of brigatinib
in ALK+ NSCLC patients with intracranial CNS metastases at baseline
was also presented at the ELCC meeting. In an independent central
radiological review of brain Magnetic Resonance Imaging (MRI)
scans, 49 of 79 ALK+ NSCLC patients in the Phase 1/2 trial were
identified to have intracranial CNS metastases at baseline. Of
these 49 patients, 16 had measurable intracranial CNS metastases
(15 evaluable) and 33 patients had only non-measurable intracranial
CNS metastases (30 evaluable).
- AEs in patients with CNS metastases
occurred at a similar incidence as in the broader study
population.
- In this post-hoc analysis of centrally
reviewed brain MRI, brigatinib demonstrated intracranial CNS
antitumor activity with responses in ALK+ NSCLC patients with
intracranial CNS metastases at baseline.
- Objective response rate (ORR) was 53%
in evaluable patients with measurable lesions (n=15), including 1
(7%) CR.
- In evaluable patients with
non-measurable lesions (n=30), ORR defined as disappearance of all
lesions was 30% (9 patients).
- For patients with a response and at
least one follow-up MRI scan (n=16), median (Kaplan-Meier [KM]
estimate) duration of intracranial response was 18.9 months. For
patients with a follow-up MRI scan (n=45), median (KM estimate)
intracranial PFS was 22.3 months.
- Median time on study for ALK+ NSCLC
patients with intracranial CNS metastases at baseline was 56.1
weeks (range, 0.1-150+ weeks).
Pivotal Phase 2 ALTA Trial Enrolling Patients
A separate, pivotal global Phase 2 trial of brigatinib (AP26113)
in patients with locally advanced or metastatic ALK+ NSCLC who have
progressed on crizotinib continues to enroll 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 are randomized 1:1 to receive either 90 mg of brigatinib
once per day continuously or a lead-in dose of 90 mg/day for 7 days
followed by 180 mg/day continuously.
“We are on track for full patient enrollment in the ALTA trial
in the third quarter of this year,” stated Frank G. Haluska, M.D.,
Ph.D., senior vice president of clinical research and development
and chief medical officer at ARIAD. “We are encouraged by the CNS
anti-tumor activity, now exceeding 18 months in the Phase 1/2
brigatinib trial, and look forward to the evaluation of activity on
brain metastasis in the ALTA trial.”
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).
Forward-Looking Statements
This press release contains forward-looking statements. Any
statements contained herein which do not describe historical facts,
including, but not limited to, statements regarding: updated
clinical data for brigatinib and the estimated timing for
completing enrollment in our ALTA clinical trial, are
forward-looking statements which 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, among others: preclinical data and early-stage clinical
data may not be replicated in later-stage clinical studies; the
costs associated with our research, development, manufacturing and
other activities; the adequacy of our capital resources and the
availability of additional funding; our ongoing and additional
clinical trials of brigatinib may not be successful or initiated,
enrolled or conducted in a timely manner; regulatory developments
and safety issues; competitive risks; manufacturing issues and
those additional 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. All
forward‐looking statements in this press release are qualified in
their entirety by this cautionary statement.
ARIAD Pharmaceuticals, Inc.For InvestorsKendra Adams,
617-503-7028Kendra.adams@ariad.comorFor MediaLiza Heapes,
617-620-4888Liza.heapes@ariad.com
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