An Open-label, Multicenter, Phase II Study of LDK378 in Patients With Non-small Cell Lung Cancer Harboring ROS1 Rearrangement

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. LDK378 is an orally highly selective and potent ALK kinase inhibitor. In preclinical studies, LDK378 has much lower IC50 values than crizotinib in cell lines engineered to express ROS1 rearrangement (0.15 nM versus 3 nM) and is approximately 20-fold more potent. LDK378 is a potent inhibitor of tumor growth in rodent models of both ALCL and NSCLC. We suggest a phase II trial of LDK378 in advanced non-small cell lung cancer patients with ROS1 rearrangement. The aim of current trial is to evaluate the antitumor efficacy and safety profile of LDK378 and to identify biomarker to predict the tumor response to LDK378.

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Key information

Conditions

Non-small Cell Lung Cancer (NSCLC) Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Yonsei Cancer Center at Yonsei University Medical Center

Seoul, 03722, South Korea

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Subjects with histologically or cytologically confirmed, unresectable NSCLC that carries a ROS1 rearrangement, as per FISH assay (Abbott Molecular Inc.)
ECOG performance status of 0 to 2
Male or female; ≥ 20 years of age
Subjects must have received at least 1 platinum doublet to treat their locally advanced or metastatic NSCLC
Subjects whose disease has progressed within 6 months Subjects with measurable lesion (using RECIST 1.1 criteria)
Subjects must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2
Subjects must have archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since
Provision of written informed consent prior to any study specific procedures

Exclusion criteria

Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy.
Any major operation or irradiation within 4 weeks of baseline disease assessment
Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms
Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ or treated thyroid cancer.
Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome, 2° or more AV Block and uncontrolled hypertension)
Pregnant or lactating female
Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

Treatment and study plan

LDK378

Drug

LDK378 750mg oral administration and continuously (28-day treatment schedule as one treatment cycle)

Primary outcomes

Overall response rate (ORR)

Time frame: 1 month after treatment

Lesions measurements are performed by CT or MRI scan, evaluation by RECIST criteria v1.1

Sponsors and collaborators

Lead sponsor

Yonsei University

Other

Registry information

Important dates

Study start: 2013
Primary completion: 2026
Study completion: 2026
First posted: Oct 17, 2013
Registry last updated: Jul 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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