ARIAD Pharma (ARIA) Presents Updated Brigatinib Phase 1/2 Data in ALK+ NSCLC; 62% Achieved Objective Response

October 10, 2016 7:36 AM EDT

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ARIAD Pharmaceuticals, Inc. (Nasdaq: ARIA) 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 PatientsData 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 PatientsData 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 EnrolledData 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.


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