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Study of Lorlatinib in ROS1 Rearranged NSCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03612154
Recruitment Status : Recruiting
First Posted : August 2, 2018
Last Update Posted : April 6, 2022
Information provided by (Responsible Party):
Ji-youn Han, National Cancer Center, Korea

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

Condition or disease Intervention/treatment Phase
Nonsmall Cell Lung Cancer Drug: Lorlatinib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Lorlatnib in ROS1 Rearranged Advanced NSCLC
Actual Study Start Date : May 2, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Lorlatinib

Arm Intervention/treatment
Experimental: Lorlatinib
Subjects will be treated with lorlatinib 100mg PO daily. A cycle will be defined as 28-days for the convenience of analysis.
Drug: Lorlatinib
Subjects will be treated with lorlatinib 100mg PO daily. A cycle will be defined as 28-days for the convenience of analysis.

Primary Outcome Measures :
  1. ORR [ 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"). ]
    To assess the clinical efficacy of lorlatinib as measured by ORR using RECIST criteria v 1.1

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

4.1. Inclusion criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03612154

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Contact: Ji-Youn Han, MD.Ph.D. 82-31-920-1154
Contact: Sung Jin Yoon, SC 82-31-920-0399

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Korea, Republic of
National Cancer Center Recruiting
Goyang-Si, Gyeonggi-do, Korea, Republic of, 10408
Contact: Ji-Youn Han, Ph.D    +82-31-920-1210   
Contact: Sung Jin Yoon    +82-31-920-0399   
Sponsors and Collaborators
National Cancer Center, Korea
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Principal Investigator: Ji-Youn Han, MD.Ph.D. National Cancer Center
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Responsible Party: Ji-youn Han, MD. PhD., National Cancer Center, Korea Identifier: NCT03612154    
Other Study ID Numbers: NCC-2018-0232
First Posted: August 2, 2018    Key Record Dates
Last Update Posted: April 6, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases