Clinical Trials /

Study of Lorlatinib in ROS1 Rearranged NSCLC



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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:



Phase 2

Trial Eligibility



  • Brief Title: Study of Lorlatinib in ROS1 Rearranged NSCLC
  • Official Title: A Phase II Study of Lorlatnib in ROS1 Rearranged Advanced NSCLC

Clinical Trial IDs

  • ORG STUDY ID: NCC-2018-0232
  • NCT ID: NCT03612154


  • Nonsmall Cell Lung Cancer




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

Detailed Description

      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-naïve 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.

Trial Arms

LorlatinibExperimentalSubjects will be treated with lorlatinib 100mg PO daily. A cycle will be defined as 28-days for the convenience of analysis.
  • Lorlatinib

Eligibility Criteria

        4.1. Inclusion criteria

          1. Metastatic or recurrent NSCLC with ROS1 rearrangement identified by NGS-based target

          2. Treatment naïve or one prior systemic treatment with platinum doublet chemotherapy

          3. At least one measurable disease lesion according to RECIST 1.1

          4. ECOG performance status 0-2

          5. Age ≥ 18 years

          6. Adequate hematologic, hepatic, and renal function

          7. Written informed consent

        4.2. Exclusion criteria

          1. Life expectancy of less than 12 weeks

          2. Prior treatment with a ROS1 inhibitor

          3. Symptomatic uncontrolled brain metastasis

          4. 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

          5. Uncontrolled intercurrent illness

          6. Pregnancy or unwillingness to use effective birth control

          7. Known hypersensitivity to lorlatinib and/or its excipients
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Time Frame:from Cycle1 Day 1 until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months").
Safety Issue:
Description:To assess the clinical efficacy of lorlatinib as measured by ORR using RECIST criteria v 1.1


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Center, Korea

Last Updated

September 10, 2020