Ariad Pharmaceuticals, Inc. (NASDAQ:ARIA) announced clinical data on brigatinib, its investigational anaplastic lymphoma kinase (ALK) inhibitor, from the ongoing Phase 1/2 and pivotal ALTA trials in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC) and intracranial central nervous system (CNS) metastases. These data, being presented today at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer (WCLC) being held in Vienna, showed that in patients with measurable brain metastases, the confirmed intracranial objective response rate (ORR) was 53 percent in the Phase 1/2 trial, and the confirmed intracranial ORR was 67 percent in Arm B (brigatinib 180 mg with seven-day lead-in at 90 mg once daily) in the ALTA trial. Median intracranial progression-free survival (PFS) in ALTA Arm B was 18.4 months.
“Although crizotinib is initially effective in most patients with advanced ALK rearranged lung cancer, patients eventually develop resistance to crizotinib, often with new or progressive brain metastases,” said presenting author Scott N. Gettinger, M.D., associate professor of medicine at Yale Cancer Center. “We are clearly encouraged by these data that demonstrate efficacy in the brain, with median intracranial PFS of over one and a half years, in patients with crizotinib refractory disease.”
The ALTA Trial
The ALTA (ALK in Lung Cancer Trial of AP26113) trial enrolled 222 patients with ALK+ NSCLC who had been treated with and experienced disease progression on their most recent crizotinib therapy. Patients were randomized one-to-one to receive either 90 mg of brigatinib once per day (QD) (Arm A), or 180 mg QD with a seven-day lead-in at 90 mg QD (Arm B). In addition, patients were stratified by presence of brain metastases at baseline and best response to prior crizotinib therapy. Patient enrollment is complete, with the last patient enrolled in September 2015. Median follow-up in all patients with intracranial CNS metastases at baseline enrolled in the ALTA trial was 10.7 months as ofMay 31, 2016.
Phase 1/2 Study
The Phase 1/2 study of brigatinib included a dose-escalation portion that enrolled patients with advanced solid tumors, particularly those with NSCLC, who were either refractory to available therapies or had no standard treatment available to them. The Phase 2 portion of the trial includes five expansion cohorts. The trial enrolled 137 patients with 79 patients having ALK+ NSCLC. All but eight ALK+ NSCLC patients had failed prior crizotinib therapy. Patient enrollment in the trial is complete, with the last patient enrolled in July 2014. Median follow-up in ALK+ NSCLC patients with intracranial CNS metastases at baseline in the Phase 1/2 study was 24.9 months as of May 31, 2016.
Key Data from Oral Presentation on Patients with Baseline CNS Metastases from Phase 1/2 and ALTA Trials
Follow-up Data as of May 31, 2016; Last IRC Data in ALTA Trial was July 13, 2016, and Last Brain Scan in Phase 1/2 Trial was October 8, 2015
- In the Phase 1/2 trial of brigatinib, 50/79 (63%) of ALK+ NSCLC patients had IRC-assessed baseline brain metastases. In the ALTA trial, 153/222 (69%) of ALK+ NSCLC patients had IRC-assessed baseline brain metastases. The efficacy analysis of Phase 1/2 trial data was based on an evaluable population (patients with at least one on-study brain scan, n=46), and the analysis of ALTA trial data was based on the intention-to-treat (ITT) population (n=153).
- As of May 31, 2016, 42 percent and 55 percent of ALK+ NSCLC patients with brain metastases at baseline remained on study in the Phase 1/2 and ALTA populations respectively.
- For patients with measurable brain lesions, the confirmed intracranial ORR was 53 percent (8/15) in the Phase 1/2 trial, and confirmed intracranial ORRs were 67 percent (12/18) in Arm B and 46 percent (12/26) in Arm A in the ALTA trial.
- There were 31 patients in the Phase 1/2 trial with only non-measurable brain lesions, and of these, 35 percent had complete resolution of lesions. In ALTA, there were 55 patients in Arm B and 54 in Arm A with only non-measurable lesions; of these, 18 percent and seven percent of patients, respectively, had complete resolution of lesions.
- For patients with any brain metastases at baseline:
- Median duration of intracranial response in confirmed responders was 11.4 months in the Phase 1/2 trial (n=19); and was not yet reached in either arm of the ALTA trial (n=22 in Arm B and n=16 in Arm A).
- Median intracranial PFS was 14.6 months in the Phase 1/2 trial (n=46); and 18.4 months (95% confidence interval [CI] 12.8 – not reached) and 15.6 months (95% CI 9.0-18.3 months) in ALTA Arm B and Arm A, respectively (n=73/n=80).
- In the Phase 1/2 trial (n=46), for patients with any brain metastases at baseline, investigator-assessed whole-body ORR was 74 percent, median duration of response was 24 months and median PFS was 14.5 months. In ALTA (Arms B and A, respectively), for patients with any brain metastases at baseline, investigator-assessed whole-body ORR was 58 percent and 39 percent, median duration of response was not yet reached and 12 months, and median PFS was 12.9 months and 9.2 months.
- In patients with any brain metastases at baseline in the ALTA trial, the most common treatment-emergent adverse events (AEs), grade 3 or higher (excluding neoplasm progression), were (n=151 treated; Arm B/A): increased creatine phosphokinase (CPK) (12%/1%), hypertension (7%/4%), increased lipase (3%/4%), malignant pleural effusion (1%/4%) and pneumonia (4%/1%).
The oral presentation, “Brigatinib Activity in Patients with ALK+ NSCLC and Intracranial CNS Metastases in Two Clinical Trials,” (Abstract #4374, Oral ID OA08.06) will be presented today, Monday, December 5, 2016 in the Schubert 1 Auditorium at 11:57 am ET/16:57 GMT. (Original Source)
Shares of Ariad Pharmaceuticals are up nearly 3% to $13.60 in pre-market trading. ARIA has a 1-year high of $14.42 and a 1-year low of $4.37. The stock’s 50-day moving average is $11 and its 200-day moving average is $9.79.
On the ratings front, ARIA stock has been the subject of a number of recent research reports. In a report issued on November 30, JMP analyst Michael King reiterated a Hold rating on ARIA. Separately, on November 17, Leerink Swann’s Michael Schmidt reiterated a Buy rating on the stock .
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Michael King and Michael Schmidt have a yearly average loss of 1.9% and a return of 24.2% respectively. King has a success rate of 42% and is ranked #3352 out of 4240 analysts, while Schmidt has a success rate of 61% and is ranked #33.
Overall, 2 research analysts have rated the stock with a Sell rating, 2 research analysts have assigned a Hold rating and 5 research analysts have given a Buy rating to the stock. When considering if perhaps the stock is under or overvalued, the average price target is $12.50 which is -5.0% under where the stock closed last Friday.
ARIAD Pharmaceuticals, Inc. operates as an oncology company, which engages in the discovery, development, and commercialization of small-molecule drugs for the treatment of cancer. Its products include Iclusig and Caregivers.