GENEVA & CAMBRIDGE, Mass.--(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.
- 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.”
ARIAD 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).
This 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.