Study of Lorlatinib in ROS1 Rearranged NSCLC

A Phase II Study of Lorlatnib in ROS1 Rearranged Advanced NSCLC

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

Study Overview

• Status: Recruiting
• Conditions: Nonsmall Cell Lung Cancer
• Intervention / Treatment: Drug: Lorlatinib

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.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ji-Youn Han, MD.Ph.D.; Phone Number: 82-31-920-1154; Email: jymama@ncc.re.kr
• Study Contact Backup: Name: Sung Jin Yoon, SC; Phone Number: 82-31-920-0399; Email: sjyoon@ncc.re.kr

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Goyang-Si, Gyeonggi-do, Korea, Republic of, 10408
      • Recruiting
      • National Cancer Center
      • Contact: Sung Jin Yoon; Phone Number: +82-31-920-0399; Email: sjyoon@ncc.re.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	To assess the clinical efficacy of lorlatinib as measured by ORR using RECIST criteria v 1.1	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").

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea
• Investigators: Principal Investigator: Ji-Youn Han, MD.Ph.D., National Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2019
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): August 2, 2018

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NCC-2018-0232

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No