ARIAD Pharmaceuticals, Inc. (ARIA) today announced updated clinical data on its investigational tyrosine kinase inhibitor (TKI), 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 current results include more mature efficacy data for brigatinib, including updated response rates and median duration of response in ALK+ NSCLC patients, as well as more extensive safety data for all patients in the trial.
The updated Phase 1/2 results were presented this morning at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
Phase 1/2 Study
The data presented at ASCO include 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 updated brigatinib data show an objective response rate of approximately 70 percent in crizotinib-resistant ALK-positive NSCLC patients,” stated D. Ross Camidge, MD, PhD, director of thoracic oncology at the Colorado University Cancer Center. “In addition, the median progression-free survival in this second-line patient group is now over the one-year mark.”
Safety and Tolerability – All Patients Enrolled
- The most common adverse events (AEs; ≥ 30%), regardless of treatment relationship, were nausea (52%), fatigue (42%), diarrhea (40%), headache (33%), and cough (32%).
- AEs, 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%), pulmonary embolism (3%), increased alanine aminotransferase (ALT) (2%), hyponatremia (2%), hypophosphatemia (2%), and malignant pericardial effusion (2%).
- 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%).
- 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%). In addition, no early-onset pulmonary events were observed in the 32 patients started at 90 mg and escalated to 180 mg after seven days.
Anti-tumor Activity – ALK+ NSCLC Patients
- Of the 78 ALK+ NSCLC patients evaluable for response, 58 (74%) demonstrated an objective response to brigatinib. Fifty responses were confirmed by repeat imaging studies. The “waterfall plot” analysis demonstrated tumor shrinkage in nearly all ALK+ NSCLC patients, with 25 patients (36%) experiencing 100% shrinkage of the target lesion.
- Of the eight evaluable TKI-naïve ALK+ NSCLC patients treated with brigatinib, all demonstrated an objective response (100%), including three complete responses (CR). Seven responses were confirmed.
- Of the 70 evaluable ALK+ NSCLC patients with prior crizotinib therapy treated with brigatinib, 50 (71%) demonstrated an objective response. Forty-three responses were confirmed.
- The median duration of response was 9.3 months in ALK+ NSCLC patients treated with prior crizotinib therapy and was not yet reached in ALK+ NSCLC patients who were crizotinib-naïve.
- Median progression-free survival (PFS) was 13.4 months in ALK+ NSCLC patients treated with prior crizotinib therapy and was not yet reached in ALK+ NSCLC patients who were crizotinib-naïve.
- An evaluation of the efficacy of brigatinib in ALK+ NSCLC patients with intracranial CNS metastases at baseline was also included in the ASCO presentation. In an independent central review of brain magnetic resonance imaging (MRI) scans, 52 of 79 ALK+ NSCLC patients were identified to have intracranial CNS metastases at baseline.
- Of these 52 patients, 17 had measurable intracranial CNS metastases (15 evaluable), and 35 patients had only non-measurable intracranial CNS metastases (33 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 ALK+ NSCLC patients with intracranial CNS metastases at baseline was 15.6 months.
Pivotal Phase 2 ALTA Trial Enrolling Patients
A separate, pivotal global Phase 2 trial of brigatinib in patients with locally advanced or metastatic ALK+ NSCLC who have progressed on crizotinib is enrolling patients. The ALTA (ALK in Lung Cancer Trial of AP26113) trial is designed to determine the safety and efficacy of brigatinib 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 expect to reach 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 duration of responses in ALK+ NSCLC patients that have emerged from the on-going Phase 1/2 brigatinib trial, reinforcing our belief that brigatinib has the potential to address a significant unmet medical need in ALK+ NSCLC patients.”
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, visithttp://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, the therapeutic potential of 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: 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.