Phase III ALTA-1L Trial Shows Promise for Patients with Non-Small Cell Lung Cancer


Takeda announced that their ongoing phase III ALTA-1L trial of brigatinib reduced the risk of disease progression or death in adults with advanced ALK-positive non-small cell lung cancer.

The ongoing phase III ALTA-1L trial of brigatinib (Alunbrig) versus crizotinib (Xalkori) suggested that brigatinib reduced the risk of disease progression or death in adults with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who had not received a prior ALK inhibitor, according to Takeda, the drug’s developer.

These data were presented during the presidential session at the 2019 European Society for Medical Oncology (ESMO) Asia Congress in Singapore. 

Results indicated that after more than 2 years of follow-up, brigatinib reduced the risk of disease progression or death by 76% (HR = 0.24; 95% CI, 0.12-0.45) in newly diagnosed patients whose disease had spread to the brain at time of enrollment. There was also a 57% reduction in risk of disease progression or death in all patients (HR = 0.43; 95% CI, 0.31-0.61).

In the global, multicenter cohort, 275 patients were randomized to receive either 180 mg of brigatinib once daily, with a 7-day lead in at 90 mg once daily, or 250 mg of crizotinib twice daily. Blinded independent review committee (BIRC)-assessed progression-free survival (PFS) was the primary endpoint. Secondary endpoints included objective response rate (ORR) per RECIST v1.1, intracranial ORR, intracranial PFS, overall survival (OS), safety, and tolerability.

“Individual treatment needs for patients with ALK-positive NSCLC are diverse because cancer is not a one-size-fits-all disease. Ongoing research and clinical trials such as ALTA-1L are critical to achieving our goal of improving outcomes and quality of life for patients early on in their treatment journey,” Bonnie Addario, co-founder and board chair of GO2 Foundation for Lung Cancer, said in a press release issued by Takeda.

Results from the trial were evaluated by 2 separate review bodies: study investigators and a BIRC. At the data cutoff for the second interim analysis, the BIRC-assessed HR of PFS was 0.49 (95% CI, 0.35-0.68; P < 0.0001).

The safety profile of brigatinib was generally consistent with the existing U.S. prescribing information. The most common adverse events (AEs) ≥25% of patients in the 90 mg group were nausea (33%), fatigue (29%), headache (28%), and dyspnea (27%). In the 180 mg group, the most common AEs were nausea (40%), diarrhea (38%), fatigue (36%), cough (34%), and headache (27%).

“We look forward to submitting these data to regulatory authorities around the globe with the goal of making Alunbrig available to ALK-positive NSCLC patients worldwide,” Philip Rowlands, PhD, Oncology Therapeutic Area Unit, Takeda Pharmaceuticals, said in a press release.

NSCLC is the most common form of lung cancer, accounting for almost 85% of all lung cancer diagnoses according to the press release. Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients. Approximately 3-5% of patients with metastatic NSCLC have a rearrangement in the ALK gene.

Takeda is currently recruiting for multiple clinical trials further evaluating the efficacy and safety of brigatinib in patients with ALK+ NSCLC.

1. Takeda Presents Long-Term Data in ALK+ NSCLC Showing ALUNBRIG® (brigatinib) Continues to Demonstrate Superiority in the First-Line After Two Years of Follow-Up. [news release] Cambridge, Massachusetts and Osaka, Japan. November 22, 2019. Accessed November 25, 2019.

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