Efficacy and safety of brigatinib in patients with ALK TKI-naive advanced ALK+ NSCLC: Integrated analysis of the ALTA-1L and J-ALTA trials

Lung Cancer. 2025 Mar:201:108424. doi: 10.1016/j.lungcan.2025.108424. Epub 2025 Feb 4.

Abstract

Objectives: Brigatinib approval as a first-line anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) for advanced ALK+ non-small cell lung cancer (NSCLC) is supported by results of a non-Japanese global phase 3 trial (ALTA-1L) and a separate phase 2 trial conducted in Japan (J-ALTA). To evaluate outcomes in a larger global patient population, we conducted an integrated analysis of pooled efficacy and safety data from ALTA-1L and J-ALTA.

Materials and methods: ALTA-1L (NCT02737501) and J-ALTA (NCT03410108) were open-label, multicenter studies of patients with advanced or metastatic ALK+ NSCLC. ALTA-1L and an expansion cohort of J-ALTA enrolled patients who were ALK TKI naive. Patients with stable or asymptomatic brain metastases were allowed. Brigatinib 180 mg was administered once daily following 7-day lead-in at 90 mg. Primary endpoints were blinded independent review committee (IRC)-assessed progression-free survival (PFS) in ALTA-1L and IRC-assessed 12-month PFS in the J-ALTA ALK TKI-naive cohort. Secondary endpoints included IRC-assessed objective response rate (ORR), duration of response (DOR), intracranial ORR, overall survival (OS), and safety.

Results: Overall, 169 patients were allocated to brigatinib in ALTA-1L (n = 137) or J-ALTA (n = 32). In the pooled population (median follow-up: 35.8 months), 34 % of patients were aged ≥65 years, 28 % had baseline brain metastases, and 26 % had received prior chemotherapy. Median PFS by IRC was 29.3 months (95 % CI: 23.9-44.7). Confirmed ORR was 79 % (95 % CI, 72 %-85 %). Median DOR was 38.1 months. Intracranial ORR was 66 % in patients with any brain metastases and 70 % in patients with measurable brain metastases. Three-year OS was 74 %. Grade 3/4 adverse events occurred in 74 % of patients, most commonly increased blood creatine phosphokinase (31 %), hypertension (18 %), and increased lipase (16 %).

Conclusion: Brigatinib demonstrated clinically meaningful systemic and intracranial efficacy in patients with ALK TKI-naive ALK+ NSCLC. Safety results were consistent with the known profile for brigatinib.

Keywords: Anaplastic lymphoma kinase; Clinical trial; Non-small cell lung cancer; Tyrosine kinase inhibitor.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase* / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase* / genetics
  • Anaplastic Lymphoma Kinase* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Organophosphorus Compounds* / adverse effects
  • Organophosphorus Compounds* / therapeutic use
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyrimidines* / adverse effects
  • Pyrimidines* / therapeutic use
  • Treatment Outcome

Substances

  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • brigatinib
  • Organophosphorus Compounds
  • Protein Kinase Inhibitors
  • Pyrimidines