This is an open-label, multicenter, randomized phase 2 trial for patients with tyrosine kinase inhibitor-naïve ALKrearranged advanced NSCLC. Subjects are initially treated with lorlatinib for 12 weeks.
Histologically or cytologically confirmed diagnosis of stage IV NSCLC (or recurrent NSCLC not a candidate for definitive multimodality therapy)
Documented ALK re-arrangement as detected by: (1) FISH, (2) IHC, (3) tissue NGS, or (4) cfDNA NGS
Subjects can be enrolled as (a) TKI naïve or (b) after/during 12 weeks of first line lorlatinib treatment without disease progression or (c) ≤4 weeks of first line alectinib, brigatinib or ensartinib treatment without disease progression, those patients must be switched to lorlatinib.
Candidate for local consolidation therapy in the opinion of the treating physician.
Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who have had at least 2 years elapsed since the completion of radical treatment and the adjuvant therapy, if any, of the other primary malignancy.
Previously received any prior TKI, including ALK-targeted TKIs. Note: on-going first line alectinib, brigatinib, lorlatinib and ensartinib use as specified in the Inclusion criteria is allowed.
Previously received more than 1 cycle of chemotherapy +/-immunotherapy for locally advanced or metastatic disease.
Symptomatic CNS metastasis. Asymptomatic CNS disease requiring increasing dose of corticosteroids within 7 days prior to study enrollment is also not permitted.