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

Launched by YONSEI UNIVERSITY · Jan 12, 2018

Keywords

ClinConnect Summary

Recently, our group found the prevalence of ROS1 rearrangement reached up to 3.2% in clinically selected population (never smokers) and 5% in genetically selected population (EGFR-/ALK-wild-type). These data strongly suggests that ROS1 rearrangement is a potential therapeutic target with relatively high incidence. In this study, investigator confirmed the presence of ROS1 fusion by RT-PCR and correlation between FISH and IHC (Cell Signaling Technology®).

LDK378 is an orally highly selective and potent ALK kinase inhibitor. In preclinical studies, LDK378 has much lower IC50 values than criz...

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Eligibility criteria

• • Inclusion criteria
• • histologically or cytologically confirmed, stage IV or recurrent NSCLC that carries a ROS1 rearrangement, as per anchored multiplex PCR
• • ECOG performance status of 0 to 2
• • Male or female≥ 20 years of age
• • treatment naive or may be allowed up to 2 prior systemic anti-cancer therapy for their stage IV or recurrent NSCLC, which includes cytotoxic chemotherapy and I-O, but excludes crizotinib.
• • measurable lesion (using RECIST 1.1 criteria)
• • measurable lesion (using RECIST 1.1 criteria)
• • archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since
• * Subjects who meet the following criteria:
• • ANC 1.5 x 109/L -Platelet 100 x 109/L
• • creatinine 1.5 x ULN
• • AST (SGOT) and ALT (SGPT) 3 x ULN (If there is Liver Metastasis 5 x ULN
• • Total bilirubin 1.5 x ULN
• • written informed consent prior to any study specific procedures
• • Leptomeningeal carcinomatosis may be included
• • Exclusion criteria
• • More than two actionable mutations
• • Patients who received prior crizotinib 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 who have CNS complications that require urgent neurosurgical intervention(e.g. resection or shunt placement)
• • Other co-existing malignancies or malignancies diagnosed within the last 3 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
• • Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention).
• * Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with LDK378 and for the duration of participation (see Appendix 1 Tables):
• • Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (please refer to http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm)
• • Strong inhibitors or strong inducers of CYP3A4/5 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org)
• • Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, CYP2C8 and/or CYP2C9 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org)
• • Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived anti-coagulant. Anticoagulants not derived from warfarin are allowed (eg, dabigatran, rivaroxaban, apixaban).
• • Unstable or increasing doses of corticosteroids
• • enzyme-inducing anticonvulsive agents
• • herbal supplements
• • Patients who have received thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy ≤ 2 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study treatment is allowed.