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TKI-naïve Advanced ALK-positive NSCLC (ALTA 1L Study)
The efficacy of brigatinib was demonstrated in a randomized (1:1), open-label, multicenter trial(ALTA 1L, NCT02737501) in adult patients with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. The study required patients to have an ALK rearrangement based on a local standard of care testing. Eligible patients were allowed to have up to1 prior regimen of chemotherapy in the locally advanced or metastatic setting and were required to have an ECOG Performance Status of 0-2. Neurologically stable patients with treated or untreated central nervous system (CNS) metastases, including leptomeningeal metastases, were eligible.
Patients with a history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis were excluded. The major efficacy outcome measure was progression-free survival (PFS) as evaluated by a Blinded Independent Review Committee (BIRC) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Additional efficacy outcome measures included confirmed overall response rate (ORR), duration of response (DOR), intracranial ORR, and intracranial DOR as evaluated by BIRC, and overall survival (OS).
A total of 275 patients were randomized to receive brigatinib 180 mg orally once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib 250 mg orally twice daily (n = 138). Of the 275 enrolled patients, 239 had positive results using the companion diagnostic test, the Vysis ALK Break Apart FISH Probe Kit; central results were negative for 20 patients and unavailable for 16 patients. Crossover from the crizotinib arm to the brigatinib arm was permitted following disease progression.
Randomization was stratified by CNS metastases (present vs absent) and prior chemotherapy use for locally advanced or metastatic disease (yes, no).
Baseline demographic characteristics of the overall study population were: median age 59 years (range: 27 to 89, 32% 65 and over), 59% White and 39% Asian, 55% female, 39% ECOG PS 0 and 56% ECOG PS 1, and 58% never smokers. The disease characteristics of the overall study population were: 93% with Stage IV disease; 27% received chemotherapy in the locally advanced or metastatic setting; 14% had received CNS radiation; 31% had bone metastases; and 20% had liver metastases. CNS metastases were present in 35% (n = 96) of patients; 41 of those patients had measurable CNS lesions.
ALTA 1L demonstrated a statistically significant improvement in PFS by BIRC. Efficacy results from this study are described in Table 7 and Figure 1.
from FDA，2022.02
