Takeda presented Phase III results Tuesday at the World Conference on Lung Cancer (WCLC) demonstrating that first-line use of Alunbrig (brigatinib) reduced the risk of disease progression or death by 51 percent versus Pfizer's Xalkori (crizotinib) in adults with advanced ALK-positive non-small-cell lung cancer (NSCLC). Data from the ALTA-1L study on Alunbrig, which is currently not approved as first-line therapy for this indication, were also simultaneously published in the NEJM.
The study involved 275 patients with ALK-positive, locally advanced or metastatic NSCLC who did not receive prior treatment with an ALK inhibitor, but may have been treated with one prior regimen of chemotherapy in the advanced setting. Patients were randomly assigned to treatment with Alunbrig once daily or Xalkori twice daily. The primary endpoint was blinded independent review committee (BIRC)-assessed progression-free survival (PFS), while secondary aims included objective response rate (ORR), intracranial ORR, intracranial PFS and overall survival. The trial is designed with two pre-specified interim analyses for the primary endpoint, including one at approximately 50 percent of planned PFS events and another at about 75 percent of planned PFS events.
Takeda reported that the ALTA-1L trial met the pre-specified threshold for superiority in the primary endpoint at the first interim analysis. The company said that while median BIRC-assessed PFS was not reached in the Alunbrig arm, the Xalkori group achieved a median PFS of 9.8 months. Investigator-assessed PFS was also not reached in the Alunbrig arm, compared to 9.2 months for Xalkori. Meanwhile, confirmed ORRs in the intent-to-treat population were 71 percent and 60 percent for Alunbrig and Xalkori, respectively, while in patients with measurable brain metastases at baseline, the confirmed intracranial ORRs were 78 percent and 29 percent, respectively.
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David Kerstein, global clinical lead for Alunbrig and head of Takeda's lung cancer clinical portfolio strategy, remarked that "the ALTA-1L data demonstrate that Alunbrig is superior to [Xalkori] in the first-line setting…with particularly pronounced activity in the brain."
Alunbrig was granted accelerated approval by the FDA in April last year for use in patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to Xalkori. Takeda obtained rights to the drug as part of its $5.2-billion takeover of Ariad Pharmaceuticals, which was finalised in February 2017.
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