ALTA-2: Phase II study of brigatinib in patients with ALK-positive, advanced non-small-cell lung cancer who progressed on alectinib or ceritinib

Future Oncol. 2021 May;17(14):1709-1719. doi: 10.2217/fon-2020-1119. Epub 2021 Feb 11.

Abstract

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved outcomes in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC). However, almost all patients eventually develop progressive disease on first-line ALK TKIs (e.g., crizotinib, alectinib and ceritinib). Brigatinib, a second-generation ALK TKI, may show efficacy in alectinib- and ceritinib-refractory ALK+ NSCLC. We describe the rationale and design of ALTA-2, a Phase II study of brigatinib in patients with locally advanced/metastatic ALK+ NSCLC and documented progressive disease on alectinib or ceritinib. The primary end point is confirmed objective response rate per independent review committee using response evaluation criteria in solid tumors version 1.1. Secondary end points include duration of response, progression-free survival, overall survival, safety and health-related quality of life.

Trial registration: ClinicalTrials.gov NCT03535740.

Keywords: alectinib; anaplastic lymphoma kinase; brigatinib; ceritinib; neoplasm drug resistance; non-small-cell lung cancer; tyrosine kinase inhibitors.

Plain Language Summary

Lay abstract Tyrosine kinase inhibitor medications (like crizotinib, alectinib or ceritinib) may work as the first treatment for people with non-small-cell lung cancer (NSCLC) that has spread to other parts of the body and has the ALK+ mutation (ALK+ NSCLC) in tumor testing. However, after a while, many people stop responding to treatment with one of these medicines. Brigatinib is a tyrosine kinase inhibitor medicine that may be effective in people with ALK+ NSCLC who have stopped responding to alectinib or ceritinib treatment. We describe the need for and design of a study of brigatinib in people with ALK+ NSCLC whose disease got worse on alectinib or ceritinib. Clinical trial registration: NCT03535740 (ClinicalTrials.gov).

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adult
  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Carbazoles / administration & dosage
  • Carbazoles / adverse effects
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Clinical Trials, Phase II as Topic
  • Disease Progression
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Organophosphorus Compounds / administration & dosage*
  • Organophosphorus Compounds / adverse effects
  • Piperidines / administration & dosage
  • Piperidines / adverse effects
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Quality of Life
  • Response Evaluation Criteria in Solid Tumors
  • Sulfones / administration & dosage
  • Sulfones / adverse effects

Substances

  • Carbazoles
  • Organophosphorus Compounds
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sulfones
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • brigatinib
  • ceritinib
  • alectinib

Associated data

  • ClinicalTrials.gov/NCT03535740