CAMBRIDGE, Mass. & COPENHAGEN--(BUSINESS WIRE)--ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced updated clinical data on its investigational tyrosine kinase inhibitor (TKI), brigatinib, in patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) from an ongoing Phase 1/2 trial.
The updated Phase 1/2 results were included in a poster presentation on Sunday, October 9 at the 41st Annual Congress of the European Society for Medical Oncology (ESMO) held in Copenhagen, Denmark.
Phase 1/2 Study
The data presented at ESMO include safety analyses on all patients in the trial (N=137) and efficacy analyses on all patients with ALK+ NSCLC (n=79). Of the 79 ALK+ NSCLC patients, all but eight had failed prior crizotinib therapy. The presentation is based on patient data as of May 2016 with a median time on brigatinib treatment for ALK+ NSCLC patients of 20.0 months (range, 0.03 – 47.4 months, ongoing). Patient enrollment in the trial is complete, with the last patient enrolled in July 2014.
“The long-term follow up on this clinical trial of brigatinib continues to show anti-tumor activity with a confirmed overall objective response rate of 62 percent in crizotinib-resistant ALK-positive NSCLC patients at all doses evaluated, and 76 percent among those patients who received the 180 mg dose regimen with a seven-day lead-in at 90 mg once daily,” stated Lyudmila A. Bazhenova, M.D., a clinical professor of medicine at the University of California San Diego Moores Cancer Center. “The median progression-free survival in this post-crizotinib ALK+ NSCLC patient group continues to exceed one year.”
Key data from the study include:
Anti-tumor Activity of Brigatinib in ALK+ NSCLC Patients
Data as of May 31, 2016
Of the 71 ALK+ NSCLC patients with prior crizotinib therapy, 44 (62%)
achieved a confirmed objective response to brigatinib.
- Of the 25 patients treated with the 180 mg dose regimen (with 90 mg lead-in), 19 (76%) achieved a confirmed objective response.
- Of the eight crizotinib-naive ALK+ NSCLC patients treated with brigatinib, all achieved an objective response (100%), including three complete responses (CR). All responses were confirmed.
- The “waterfall plot” analysis demonstrated 100 percent tumor shrinkage of target lesions in 24 (33%) of 72 evaluable ALK+ NSCLC patients.
- The median duration of response in confirmed responders was 14.5 months in ALK+ NSCLC patients treated with prior crizotinib therapy and was not yet reached in ALK+ NSCLC patients who were crizotinib-naive.
- Median progression-free survival (PFS) was 12.9 months in ALK+ NSCLC patients with prior crizotinib therapy and was not yet reached in ALK+ NSCLC patients who were crizotinib-naive. The longest time on treatment for a patient who was crizotinib-naive was 47.4 months.
- The probability of overall survival (OS) at one year was 77 percent in ALK+ NSCLC patients who received prior crizotinib therapy (projected two-year OS was 61%) and 100 percent in patients who were crizotinib-naive (projected two-year OS was 100%).
CNS Anti-tumor Activity of Brigatinib in ALK+ NSCLC Patients
Data as of October 8, 2015
An evaluation of the efficacy of brigatinib in ALK+ NSCLC patients
with intracranial CNS metastases at baseline was also included in the
poster. In an independent central review of brain magnetic resonance
imaging (MRI) scans, 46 ALK+ NSCLC patients were evaluable for
intracranial response, including 15 who had measurable intracranial
CNS metastases at baseline, and 31 patients who had only
non-measurable intracranial CNS metastases.
- 10 of 15 (67%) patients with measurable intracranial CNS metastases had an intracranial objective response, and 13 of 31 (42%) with only non-measurable intracranial CNS metastases had complete disappearance of intracranial lesions.
- Median intracranial PFS for ALK+ NSCLC patients with intracranial CNS metastases at baseline was 14.6 months. Median duration of intracranial response in confirmed responders was 11.4 months.
Safety and Tolerability – All Patients Enrolled
Data as of May 31, 2016
- The most common treatment-emergent adverse events (AEs; ≥ 30%), regardless of relationship to treatment, were nausea (53%), fatigue (45%), diarrhea (42%), headache (35%), and cough (33%).
- Treatment-emergent AEs, regardless of relationship to treatment, grade 3 or higher, occurring in ≥4 percent of patients (excluding disease progression) were increased lipase (12%), pneumonia (7%), dyspnea (6%), hypoxia (6%), hypertension (5%), increased amylase (4%), fatigue (4%), hypophosphatemia (4%), and hyponatremia (4%).
- Serious treatment-emergent AEs, regardless of relationship to treatment, occurring in ≥2 percent of patients (excluding disease progression) were pneumonia (7%), dyspnea (6%), hypoxia (5%), pneumonitis (3%), pulmonary embolism (3%), confusional state (2%), malignant pericardial effusion (2%), and seizure (2%).
A subset of pulmonary AEs (including dyspnea, hypoxia, pneumonia
and/or pneumonitis) was observed to occur within seven days of
treatment initiation or treatment re-initiation following a prolonged
dose interruption. Most events occurred within 48 hours of dosing and
were generally managed with dose interruption or discontinuation and
empiric treatment (steroids and/or antibiotics).
- Rates of these AEs were numerically lower with lower starting doses (11/137 (8%), overall)
- 6/44 (14%) in patients started at 180 mg qd
- 1/50 (2%) in patients started at 90 mg qd
- Among 32 patients treated with 90 mg qd for seven days followed by 180 mg qd, no such events were reported after dose escalation.
- Administration of brigatinib at 180 mg with a seven-day lead-in at 90 mg appears not to be associated with an increased risk of additional early pulmonary AEs, when compared with continuous administration of brigatinib at 90 mg.
Brigatinib is an investigational, targeted cancer medicine discovered internally at ARIAD. It is in development for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) non-small cell cancer (NSCLC). The global Phase 2 ALTA trial, designed to determine the safety and efficacy of brigatinib in refractory ALK+ NSCLC patients who have been treated with and progressed on their most recent crizotinib therapy, is the basis for brigatinib’s initial regulatory review. ARIAD has also initiated the Phase 3 ALTA 1L trial to assess the efficacy and safety of brigatinib in comparison to crizotinib in patients with locally advanced or metastatic ALK+ NSCLC who have not received prior treatment with an ALK inhibitor. More information on brigatinib clinical trials, including the expanded access program (EAP) for ALK+ NSCLC can be found here.
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts is focused on discovering, developing and commercializing precision therapies for patients with rare cancers. ARIAD is working on new medicines to advance the treatment of rare forms of chronic and acute leukemia, lung cancer and other rare 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. Any statements contained herein which do not describe historical facts, including, but not limited to, statements regarding: updated clinical data for brigatinib and the therapeutic potential of brigatinib, 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, but are not limited to, our ability to successfully commercialize and generate profits from sales of our products; 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; competition from alternative therapies; our reliance on the performance of third-party manufacturers and specialty pharmacies or our collaborators 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.