Study of Lorlatinib in ROS1 Rearranged NSCLC

NCT ID: NCT03612154

Last Updated: 2022-04-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-02
• Study Completion Date: 2023-12-31

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.

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.

Conditions

Nonsmall Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lorlatinib

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

Group Type: EXPERIMENTAL

Lorlatinib

Intervention Type: DRUG

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

Interventions

Lorlatinib

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

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Center, Korea

OTHER_GOV

Sponsor Role: lead

Responsible Party

Ji-youn Han

MD. PhD.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ji-Youn Han, MD.Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Center

Locations

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Ji-Youn Han, MD.Ph.D.

Role: CONTACT

jymama@ncc.re.kr

82-31-920-1154

Sung Jin Yoon, SC

Role: CONTACT

sjyoon@ncc.re.kr

82-31-920-0399

Facility Contacts

Ji-Youn Han, Ph.D

Role: primary

jymama@ncc.re.kr

+82-31-920-1210

Sung Jin Yoon

Role: backup

sjyoon@ncc.re.kr

+82-31-920-0399

Other Identifiers

NCC-2018-0232

Identifier Type: -

Identifier Source: org_study_id