Ariad Pharmaceuticals, Inc. (NASDAQ:ARIA) 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.”
Key data from the study include:
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 theASCO 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.” (Original Source)
Shares of Ariad Pharmaceuticals opened today at $9.2 and are currently trading down at $9.08. ARIA has a 1-year high of $9.89 and a 1-year low of $4.90. The stock’s 50-day moving average is $9.04 and its 200-day moving average is $7.70.
On the ratings front, Ariad Pharmaceuticals has been the subject of a number of recent research reports. In a report issued on May 14, BMO analyst Jim Birchenough reiterated a Buy rating on ARIA, with a price target of $14, which represents a potential upside of 52.2% from where the stock is currently trading. Separately, on May 8, UBS’s Andrew Peters reiterated a Hold rating on the stock and has a price target of $9.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Jim Birchenough and Andrew Peters have a total average return of 42.3% and 18.2% respectively. Birchenough has a success rate of 67.3% and is ranked #13 out of 3610 analysts, while Peters has a success rate of 53.8% and is ranked #1015.
ARIAD Pharmaceuticals Inc is an oncology company. The Company is engaged in transforming the lives of cancer patients with breakthrough medicines. It commercializes & develops products and product candidates including Iclusig, Brigatinib, and AP32788.