Study of Lorlatinib in ROS1 Rearranged NSCLC

  • End date
    Dec 31, 2023
  • participants needed
  • sponsor
    National Cancer Center, Korea
Updated on 25 January 2021
measurable disease
cancer chemotherapy
platinum doublet
kidney function test
recurrent non-small cell lung cancer
proto-oncogene tyrosine-protein kinase ros


This is a phase II, multi-center, single arm study of lorlarinib as a single agent in patients with ROS1-rearranged advanced NSCLC.


ROS1 rearrangement characterizes a small subset (1-2%) of non-small cell lung cancer (NSCLC) and is associated with light or never smoking patients and adenocarcinoma histology. Recently, ROS1 inhibitors such as crizotinib and ceritinib demonstrated significant efficacy in ROS1 rearranged NSCLC. Thus, identification of ROS1 rearrangement in NSCLC is mandatory to permit ROS1 targeted therapy. However, current guidelines either do not refer to ROS1 testing or mention it briefly without making any strong recommendation. The detection of ROS1rearrangement is based on in situ (immunohistochemistry [IHC], fluorescence in situ hybridization [FISH]) and extractive non-in situ assays. While FISH still represents the gold standard in clinical trials, this technique may fail to recognize rearrangements of ROS1 with some gene fusion partner. On the other hand, IHC is the most cost-effective screening technique, but it seems to be characterized by low specificity. Extractive molecular assays are expensive and laborious methods, but they specifically recognize almost all ROS1 fusions using a limited amount of mRNA even from formalin-fixed, paraffin-embedded tumor tissues. Recently, Korean Heath Insurance Review and Assessment Service (HIRA) approved next generation sequencing (NGS)-based target sequencing for NSCLC patients, which may facilitate the detection of ROS1 rearrangement in Korean patients with advanced NSCLC.

Lorlatinib is a new, potent, brain-penetrant, ATP-competitive small molecule inhibiter of ALK/ROS1. However, the objective response rate (ORR) was 17/47 (36.2%; 95% CI 22.7, 51.5) in ROS1 arm of B7461001 study, but this result may not represent the ORR of lorlatinib as a 1st line treatment since 53% had central nervous system involvement at baseline and 72% of patients had received prior crizotinib. Therefore, given the activity of lorlatinib in ROS1 rearranged lung cancer, The investigator will investigate the efficacy of lorlatinib in ROS1 inhibitor-nave patients with ROS1- rearranged NSCLC. The investigator will also investigate the efficacy according to fusion partners and resistance mechanisms. Finally, The investigator will compare the concordance among diagnostic tests including FISH, IHC and NGS-based target sequencing and provide the clinical guidance for diagnosis of ROS1 rearrangement in NSCLC.

Condition Non-Small Cell Lung Cancer, nsclc
Treatment Lorlatinib
Clinical Study IdentifierNCT03612154
SponsorNational Cancer Center, Korea
Last Modified on25 January 2021


Yes No Not Sure

Inclusion Criteria

Metastatic or recurrent NSCLC with ROS1 rearrangement identified by NGS-based target sequencing
Treatment nave or one prior systemic treatment with platinum doublet chemotherapy
At least one measurable disease lesion according to RECIST 1.1
ECOG performance status 0-2
Age 18 years
Adequate hematologic, hepatic, and renal function
Written informed consent

Exclusion Criteria

Life expectancy of less than 12 weeks
Prior treatment with a ROS1 inhibitor
Symptomatic uncontrolled brain metastasis
Other malignancy within 5 years, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
Uncontrolled intercurrent illness
Pregnancy or unwillingness to use effective birth control
Known hypersensitivity to lorlatinib and/or its excipients
Clear my responses

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