Phase II data of brigantinib for relapsed and metastatic NSCLC released

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The targeted diseaseData from the pivotal Phase 2 ALTA clinical trial evaluating brigatinib in patients with crizotinib-refractory, anaplastic lymphoma kinase-positive (ALK ) locally advanced or metastatic non-small cell lung cancer (NSCLC) were published in the Journal of Clinical Oncology.

The study found that, for the patients who received brigatinib at 180 mg once daily following a seven-day lead-in at 90 mg once daily, the Independent Review Committee (IRC) assessed confirmed objective response rate (ORR) was 53 percent.

Additionally, 67 percent of patients with measurable brain metastases who received this dosing regimen achieved a confirmed intracranial objective response.

Takeda recently received accelerated approval from the U.S. Food and Drug Administration (FDA) for this indication, and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

“Given that half of ALK NSCLC patients treated with crizotinib will progress within one year, in many cases with cancer spreading to the brain, it is critical that we have new effective therapies that can address these mechanisms of resistance,” said presenting author Dong-Wan Kim, M.D., Ph.D., head of the Cancer Clinical Trials Center at the Seoul National University Hospital in South Korea. “The ALTA trial results offer clinicians important information on the efficacy and safety of brigatinib in patients who have progressed on crizotinib, and show brigatinib to be highly effective in this setting, both systemically and in the brain.”

ALTA, a two-arm, open-label, multicenter trial, enrolled 222 patients with locally advanced or metastatic ALK NSCLC who had progressed on crizotinib, the current standard of care for first line treatment in the metastatic setting.

Patients were randomised one-to-one to receive either 90 mg of brigatinib once per day (90 mg; Arm A), or 180-mg once daily with a seven-day lead-in at 90 mg once daily (the 180 mg regimen; Arm B).

In addition, patients were stratified by the presence of brain metastases at baseline and best response to prior treatment with crizotinib.

The primary efficacy outcome measure was confirmed ORR according to RECIST v1.1 as evaluated by the investigator.

Secondary efficacy outcome measures included confirmed ORR as assessed by an Independent Review Committee (IRC), duration of response (DOR), progression free survival (PFS), intracranial ORR, intracranial DOR, overall survival, safety and tolerability.

Efficacy outcomes favoured Arm B (the recommended dosing regimen in the full Prescribing Information) most notably in PFS and intracranial ORR.

  • With a median follow-up period of approximately 8 months (range (0.1-20.2 months), the IRC-assessed confirmed ORR was 48 percent in Arm A and 53 percent in Arm B. Investigator-assessed confirmed ORR was 45 percent in Arm A and 54 percent in Arm B.
  • The median DOR was 13.8 months in both arms as assessed by the IRC. The investigator assessed median DOR was 13.8 months in Arm A and 11.1 months in Arm B.
  • IRC-assessed median PFS was 9.2 months in Arm A and 15.6 months in Arm B. Investigator-assessed median PFS was 9.2 months and 12.9 in Arms A and B, respectively.
  • Responses in Arm B included a confirmed partial response in a patient with the ALK kinase domain G1202R mutation at baseline, that is associated with resistance to all approved tyrosine kinase inhibitors (TKIs).
  • Of the patients with measurable brain metastases at baseline, 42 percent (11/26) in Arm A and 67 percent (12/18) in Arm B achieved a confirmed intracranial OR by IRC assessment.
  • In patients with any brain metastases at baseline the median intracranial PFS as assessed by the IRC was 15.6 months and 12.8 months in Arms A and B, respectively.
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