LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib

Novartis

Status and phase: Completed; Phase 3

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: Pemetrexed; Drug: Ceritinib; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01828112

2012-005637-36 (EudraCT Number)

CLDK378A2303

Details and patient eligibility

About

The primary purpose of the study was to compare the antitumor activity of LDK378 vs. chemotherapy in patients previously treated with chemotherapy (platinum doublet) and crizotinib. Patients in the chemotherapy arm were given the option to switch to LDK378 after confirmed progressive disease (PD), while also had the choice to continue with pemetrexed treatment.

Full description

A total of 231 patients were randomized to one of the two treatment arms in a 1:1 ratio. Randomization was stratified by World Health Organization (WHO) performance status (0 versus 1-2) and whether the patient had brain metastases at screening. The study was planned to be ended once the final overall survival (OS) analysis was performed (at the earliest of approximately 196 deaths observed or statistical significance reached at earlier OS interim analysis).

Following an agreement between Novartis and European Medicines Agency (EMA) in May 2023 to terminate the trial earlier, this study was completed when the total number of deaths was 190. Patients who had Response Evaluation Criteria In Solid Tumors (RECIST)-defined disease progression as confirmed by the Blinded Independent Review Committee (BIRC), but who, in the opinion of the Investigator, had continued clinical benefit from study treatment on either the chemotherapy arm or the ceritinib arm, continued to receive treatment. These patients continued assessments in the treatment phase. In addition, only patients randomized to the chemotherapy arm were allowed to crossover to receive ceritinib therapy (extension treatment [ET] phase) after BIRC-confirmed, RECIST-defined disease progression, and provided they met the eligibility requirements.

Enrollment: 231 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patient has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as assessed by the FDA approved Abbott FISH Test.
2. Patient has stage IIIB or IV diagnosis and must have received one or two prior regimens (including platinum- doublet) of cytotoxic chemotherapy for the treatment of locally advanced or metastatic NSCLC.
3. Patient has at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation
4. Patients must have received previous treatment with crizotinib for the treatment of locally advanced or metastatic NSCLC.

Exclusion criteria

1. Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
2. Patient with a history of severe hypersensitivity reaction to pemetrexed or docetaxel or any known excipients of these drugs.
3. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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231 participants in 2 patient groups

Ceritinib

Experimental group

Description:

Ceritinib 750 mg

Treatment:

Drug: Ceritinib

Chemotherapy

Active Comparator group

Description:

Chemotherapy as determined by BIRC

Treatment:

Drug: Docetaxel

Drug: Pemetrexed