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A Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

NCT03399487 · Status: UNKNOWN · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 46

Last updated 2019-01-11

No results posted yet for this study

Summary

Lung cancer is the most leading cause of cancer-related mortality worldwide. Most of the patients with lung cancer are advanced stage at the time of diagnosis.

The two oncogenes that are important in lung cancer are epidermal growth factor receptor (EGFR) and K-ras, mutated in 10% and 15% of non-small cell lung cancer (NSCLC) patients. Large-scale DNA sequencing efforts have identified mutations in BRAF, PI3KCA and ERBB2 that together represent another 5% of NSCLC patients. The success of EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib or erlotinib, and more recently ALK/MET TKI, crizotinib, highlights the need to develop more genetically matched therapies. Therefore, genetic classification of lung cancer has become increasingly important along with the advances with targeted therapies.

ROS1 is a receptor tyrosine kinase with constitutive kinase activity. ROS1 was previously discovered in cell lines where ROS1 fused with other proteins to act as a driver oncogene. In 2007, Rikova et al reported ROS1 fusion as driver mutations in NSCLC cell line (HCC78; SLC34A2-ROS1) and NSCLC patient (CD74-ROS1). Li et al also found about 1% of samples harboring CD74-ROS1 fusion in 202 resected lung adenocarcinomas from never smokers. The incidence was as high as 10% in East Asian population. Currently there are now at least 13 ROS1 fusion variants involving 8 fusion partners (CD74-, SLC34A2-, FIG-, TPM3-, SDC4-, LRIG3-, ERZ-, KDERL2-) identified in ROS1 positive NSCLC.

Interestingly, preclinical and clinical data have shown ROS1-positive tumors are sensitive to crizotinib, because of potentially high common amino acid residues in the kinase domain between ALK and ROS1, which explain why crizotinib can inhibit both ROS1 and ALK to similar extent. Preliminary report from a phase I clinical trial of crizotinib in the ROS1-positive NSCLC expansion cohort showed an overall response rate (ORR) of 57%. Given that crizotinib has made remarkable clinical outcomes in phase I trial of ALK-positive NSCLC patients, clinical development of ROS1 inhibitors, including crizotinib, should be accelerated to provide targeted therapies to ROS1-positive NSCLC patients.

Conditions

  • Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

Interventions

DRUG

LDK378(Ceritinib)

This study is a phase II, single-arm, open label study. All participating patients must sign on the written informed consent form, and a separate form of consent will be used for the use of tissue for the biomarker research. This clinical study is targeted for the patients who harbor ROS1 rearrangement and all patients will be treated with LDK378 750mg daily. The treatment period begins on Day 1 of Cycle 1 and 1 cycle consists of 28 days.

Sponsors & Collaborators

  • Yonsei University

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
20 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-07-24
Primary Completion
2020-05-31
Completion
2020-10-31

Countries

  • South Korea

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03399487 on ClinicalTrials.gov