Clinical data on brigatinib, an investigational anaplastic lymphoma kinase (ALK) inhibitor, has been published in The Lancet Oncology. 

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 lung cancer (NSCLC).

The global Phase 2 ALTA trial, in patients with locally advanced or metastatic ALK NSCLC who were previously treated with crizotinib, is the primary 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.

“The publication reports the results of the first clinical evaluation of brigatinib in patients with advanced malignancies, including ALK NSCLC,” stated Scott N. Gettinger, M.D., associate professor of medicine at Yale Cancer Center and lead author. “Brigatinib yielded responses in the majority of patients with crizotinib-treated ALK NSCLC, with median progression free survival of over one year. Additionally, responses in the brain were achieved in this crizotinib refractory population. Early onset pulmonary adverse events, which occurred in eight percent of patients, generally within 48 hours of first dose, appeared to be related to starting dose.”

The data published this week 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 previously been treated with crizotinib.

With patient data as of June 2015, the median time on treatment for ALK NSCLC patients was 15.4 months (range, 0.03 – 39.4 months, ongoing).

The confirmed objective response rate (ORR) was 62% (44/71) in ALK NSCLC patients with prior crizotinib treatment.

The median progression free survival (PFS) of ALK NSCLC patients previously treated with crizotinib was 13.2 months.

Eight ALK NSCLC patients in the trial were crizotinib-naive.

Of these, all eight achieved a confirmed objective response, including three complete responses.

At the time of analysis, median PFS was not reached in these patients.

Brain metastases were identified in 63% of ALK NSCLC patients (50/79) at baseline.

The intracranial ORR was 53% (8/15) among evaluable patients with measurable brain metastases.

The most common grade 3–4 treatment-emergent adverse events across all doses were increased lipase (9%; 12/137), dyspnea (6%; 8/137), and hypertension (5%; 7/137).

Serious treatment-emergent adverse events (excluding neoplasm progression) reported in ≥5% of all patients were dyspnea (7%; 10/137), pneumonia (7%; 9/137), and hypoxia (5%; 7/137).

Eight percent of patients (11/137) experienced a subset of pulmonary adverse events with early onset, most occurring within 48 hours of dosing.

The frequency of these events appeared dose-related.

Among patients who started at 90 mg once daily and continued at this dose or escalated to 180 mg once daily after seven days, 2% (1/50) had such events.

ARIAD has submitted a New Drug Application (NDA) for brigatinib to the U.S. Food and Drug Administration (FDA), seeking U.S. marketing approval for patients with metastatic ALK-positive (ALK ) non-small cell lung cancer (NSCLC) who are resistant or intolerant to crizotinib.

Source: The Lancet Oncology