Lorlatinib After Failure of First-line TKI in Patients With Advanced ROS1-positive NSCLC (ALBATROS)
Status:
Recruiting
Trial end date:
2026-12-01
Target enrollment:
Participant gender:
Summary
ROS1 rearrangements are present in 1-2% of NSCLC cases and define a distinct molecular
subgroup. Like ALK (anaplastic lymphoma kinase) rearrangements in NSCLC, ROS1 fusions confer
sensitivity to the inhibitor crizotinib. Crizotinib, which is a tyrosine kinase inhibitor
(TKI), has been shown to be effective in tumors in several retrospective studies.
Recently the FDA approved entrectinib for the treatment of patients with ROS1-positive
metastatic NSCLC. This indication is based on the results of pooled data from several trials.
Together, these studies demonstrate the efficacy for entrectinib across a variety of solid
tumor types including NSCLC with ROS1 fusion.
However, despite the efficacy of crizotinib or entrectinib in ROS1-positive NSCLC, patients
will develop resistance to these tyrosine kinase inhibitors.
Lorlatinib is a new and potent ROS1 / ALK inhibitor optimized to penetrate the blood-brain
barrier. A recent study has investigated the activity of lorlatinib against the
crizotinib-resistant ROS1G2032R mutation. In this situation, lorlatinib effectively inhibited
the catalytic activity of recombinant ROS1G2032R resulting in an antiproliferative response.
Because of its potency as an ROS1 inhibitor and its ability to suppress the resistant ROS1
mutations, lorlatinib could be a treatment of choice in ROS1-positive NSCLC.
Phase:
Phase 2
Details
Lead Sponsor:
Intergroupe Francophone de Cancerologie Thoracique