Official Title
An Open-label, Multi-center, Expanded Treatment Protocol (ETP) of Oral LDK378 in Adult Patients With Non-small Cell Lung Cancer (NSCLC) Characterized by ALK Positivity
Brief Summary

Novartis-sponsored, open-label, multi-center, interventional ETP to provide LDK378 to patients with ALK (+)NSCLC, who have been pre-treated with an ALK inhibitor; except in countries where ALK inhibitors are not approved or available. The protocol will further evaluate the safety of LDK378 in patients with ALK(+) NSCLC.

Treatment IND/Protocol
Non-small Cell Lung Cancer (NSCLC)

Drug: LDK378
750 mg. orally

Eligibility Criteria

Inclusion Criteria (patients eligible for inclusion in this early treatment protocol have
to meet all of the following criteria):

1. Histologically or cytologically confirmed diagnosis of NSCLC that demonstrates ALK positivity as assessed by approved FISH test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); or the Ventana IHC test. If documentation of ALK positivity is not available, the test to confirm ALK positivity must be performed according to the above criterion, using a new tumor biopsy obtained prior to the first dose of ETP treatment (LDK378).

2. Stage IIIB or IV NSCLC patient with documented disease progression at enrollment, and who does not qualify or have access to LDK378 through a clinical trial.

3. Age 18 years or older at the time of informed consent.

4. WHO performance status 0-3.

5. Patients who have been pre-treated with an ALK inhibitor for locally advanced or metastatic NSCLC. Patients may be enrolled without prior exposure to an ALK inhibitor in countries where ALK inhibitors are not approved or available. Exposure to prior chemotherapy is not required.

6. Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2 (CTCAE v 4.03), provided that concomitant medication is given prior to initiation of treatment with LDK378. Exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment.

7. The following laboratory criteria have been met: - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L - Hemoglobin (Hgb) ≥ 8 g/dL - Platelets ≥ 75 x 109/L - Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN), except for patients with Gilbert's syndrome who may be included if total bilirubin ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN - Aspartate transaminase (AST) < 3.0 x ULN, except for patients with liver metastasis, who are only included if AST < 5 x ULN; alanine transaminase (ALT) < 3.0 x ULN, except for patients with liver metastasis, who are only included if ALT < 5 x ULN. - Calculated or measured creatinine clearance (CrCL) ≥ 30 mL/min

8. Patient must have the following laboratory values or have the following laboratory values corrected with supplements to be within normal limits at screening: - Potassium ≥ LLN - Magnesium ≥ LLN - Phosphorus ≥ LLN - Total calcium (corrected for serum albumin) ≥ LLN

9. Written informed consent for the ETP protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.

10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other ETP procedures.

Exclusion Criteria (patients eligible for this ETP must not meet any of the following

1. Patients with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).

2. Patients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to ETP entry to manage CNS symptoms.

3. Prior therapy with LDK378.

4. The patient is less than 5 half-lives from prior ALK inhibitor or targeted therapy (for adequate wash-out) without recovery from treatment toxicities to ≤ grade 1 or to their pretreatment levels.

5. Chemotherapy or an investigational therapy ≤ 3 weeks prior to starting the LDK378 treatment who have not recovered from side effects of such treatment toxicities to ≤ grade 2 or to their pre- treatment toxicities levels, with the exception of liver and cardiac functions which must be ≤ grade 1.

6. 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 LDK378 treatment or have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting LDK378 treatment is allowed.

7. Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior (2 weeks for resection of brain metastases) to starting LDK378 treatment or who have not recovered from side effects of such procedures. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery, and patients can be enrolled in the ETP ≥ 2 weeks after the procedure.

8. Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.

9. 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).

10. Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as: - unstable angina within 6 months prior to screening; - myocardial infarction within 6 months prior to screening; - history of documented congestive heart failure (New York Heart Association functional classification III-IV); - uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication - - initiation or adjustment of antihypertensive medication(s) is allowed prior to screening; - ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication; - other cardiac arrhythmia not controlled with medication; - corrected QTc > 450 msec using Fridericia correction on the screening ECG

11. Impaired GI function or GI disease that may alter absorption of LDK378 or inability to swallow up to five LDK378 capsules daily

12. Ongoing GI adverse events > grade 2 (e.g. nausea, vomiting, or diarrhea) at the start of the ETP.

13. 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 the ETP participation (see Appendix 1: Tables 14-1, Table 14-2, Table 14-3, and Table 14-4): - Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (please refer to - Strong inhibitors or strong inducers of CYP3A4/5 (please refer to or - Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, CYP2C8 and/or CYP2C9 (please refer to or - 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

14. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

15. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after the last dose of study treatment. In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

16. Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of study treatment. Male patients for 3 months should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

Eligibility Gender
Eligibility Age
Minimum: 18 Years
Hong Kong
Korea, Republic of
United States

Ironwood Cancer and Research Centers
Chandler, Arizona, 85224


Contact: 480-855-2225

Investigator: Sujith R Kalmadi

Banner MDACC
Gilbert, Arizona, 85234


Contact: 480-256-3333

Investigator: Klaus Wagner

Western Regional Medical Center, Inc.
Goodyear, Arizona, 85338


Contact: 602-358-8400

Investigator: Glen Weiss

Highlands Oncology Group
Fayetteville, Arkansas, 72703


Contact: 479-587-1700

Investigator: Eric S Schaefer

City of Hope National Medical Center
Duarte, California, 91010


Contact: +1 626 256 4673 Ext 85013

Investigator: Marianna Koczywas

Moores UCSD Cancer Center
La Jolla, California, 92093


Contact: 858-822-6267

Investigator: Lyudmila Bazhenova

St Joseph Heritage Healthcare
Santa Rosa, California, 94503


Contact: 707-542-2783

Investigator: Ian Anderson

Stanford University
Stanford, California, 94305-5203


Contact: 650-725-3973

Investigator: Heather Ann Wakelee

Eastern Connecticut Hematology & Oncology Associates
Norwich, Connecticut, 06360


Contact: 860-886-8362

Investigator: Dennis E. Slater

Advanced Medical Specialties
Miami, Florida, 33176


Contact: 305-595-2141

Investigator: Paul Kaywin

Peachtree Hematology/Oncology Consultants
Atlanta, Georgia, 30309


Contact: 512-421-4163

Investigator: Charles Henderson

Emory University School of Medicine/Winship Cancer Institute
Atlanta, Georgia, 30322


Contact: 404-712-2587

Investigator: Suchita Pakkala

Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611


Contact: 312-695-1379

Investigator: Jyoti D. Patel

Indiana University Health Goshen Center for Cancer
Goshen, Indiana, 46526


Contact: 574-535-2888

Investigator: Ebenezer Kio

Johns Hopkins Bayview Hospital
Baltimore, Maryland, 21224


Contact: 410-550-1117

Investigator: Rodrigo Erlich

Maryland Oncology Hematology, P.A.
Rockville, Maryland, 20850


Contact: 301-424-6231

Investigator: Nicholas Farrell

Massachusetts General Hospital Mass General
Boston, Massachusetts, 02114


Contact: 617-643-2208

Investigator: Alice Shaw

Karmanos Cancer Institute
Detroit, Michigan, 48201


Contact: 313-576-9454

Investigator: Shirish M. Gadgeel

Jackson Oncology Associates
Jackson, Mississippi, 39202


Contact: 601-974-5547

Investigator: Bobby L. Graham

Nebraska Cancer Specialist/Missouri Valley Cancer Consortium
Omaha, Nebraska, 68106


Contact: 402-991-8070

Investigator: Gamini S Soori

Hackensack University Medical Center
Hackensack, New Jersey, 07601


Contact: 201-996-2000

Investigator: Martin E. Gutierrez

Mercy Clinic Oklahoma Communities Mercy Oncology
Oklahoma City, Oklahoma, 73120-9391


Contact: 954-659-5579

Investigator: Jess F. Armor

Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111


Contact: 215-728-3545

Investigator: Ranee Mehra

Tennessee Cancer Specialists
Knoxville, Tennessee, 37909


Contact: 865-632-5122

Investigator: Russell F DeVore

University of Utah / Huntsman Cancer Institute
Salt Lake City, Utah, 84112-5820


Contact: 801-585-5318

Investigator: Sunil Sharma

Seattle Cancer Care Alliance
Seattle, Washington, 98109-1023


Contact: 206-288-2171

Investigator: Christina Baik

University of Wisconsin
Madison, Wisconsin, 53705-2397


Investigator: Ticiana Leal


Novartis Pharmaceuticals

Novartis Pharmaceuticals

Novartis Pharmaceuticals
NCT Number
MeSH Terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung