LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

Novartis

Status and phase: Completed; Phase 3

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: Ceritinib; Drug: Carboplatin; Drug: Pemetrexed; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01828099

2013-000319-26 (EudraCT Number)

CLDK378A2301

Details and patient eligibility

About

To compare the efficacy and safety of ceritinib with standard first-line chemotherapy (pemetrexed plus cisplatin or carboplatin) in patients with stage IIIB (not candidates for definitive multimodality therapy) or stage IV, non-squamous non-small cell lung cancer (NSCLC) harboring a confirmed anaplastic lymphoma kinase (ALK) rearrangement, using the Ventana immunohistochemistry (IHC) test.

Full description

This was an open-label, randomized, global, Phase III study that compared the efficacy and safety of ceritinib to standard first-line chemotherapy in patients with advanced (NSCLC) harboring ALK rearrangement. The confirmation of ALK rearrangement was done using the ICH test by a Novartis designated central laboratory. Prior to the study, patients had not received any previous systemic, anti-cancer therapy, including ALK inhibitors, for newly diagnosed advanced non-squamous NSCLC.

The patients were randomized in a 1:1 ratio to either receive ceritinib (750 mg once daily, fasted) or chemotherapy. The chemotherapy regimen consisted of a platinum-based doublet with pemetrexed followed by pemetrexed maintenance in patients without progressive disease after 4 cycles.

Treatment was continued until the blinded independent review committee (BIRC) confirmed disease progression based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), occurrence of unacceptable toxicity, or meeting other discontinuation criteria. Patients in either arm were permitted to continue the assigned study treatment beyond BIRC-confirmed disease progression in case of continued clinical benefit, as determined by the Investigator.

All patients who discontinued treatment during the treatment phase for reasons other than death, lost to follow-up, pregnancy or disease progression entered the post-treatment follow-up period until disease progression, withdrawal of consent or death.

In the chemotherapy arm, patients were allowed to switch and receive ceritinib after BIRC-confirmed disease progression (extension-treatment period).

Enrollment: 376 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. The patient had a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that was Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test was performed at Novartis designated central laboratories.
2. The patient had a newly diagnosed stage IIIB (who was not a candidate for definitive multimodality therapy) or stage IV NSCLC or relapsed locally advanced or metastatic NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted therapies, either experimental or not), with the exception of neo-adjuvant or adjuvant therapy.
3. The patient had at least one measurable lesion as defined by RECIST 1.1.

Key Exclusion Criteria:

1. The patient had known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide, and magnesium stearate).
2. The patient had a history of severe hypersensitivity reaction to platinum-containing drugs, pemetrexed, or any known excipients of these drugs.
3. The patient had symptomatic central nervous system (CNS) metastases and was neurologically unstable or had 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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376 participants in 2 patient groups

Ceritinib

Experimental group

Description:

Ceritinib administered continuously through oral dosing at a dosage of 750 mg once daily in fasted state.

Treatment:

Drug: Ceritinib

Chemotherapy

Active Comparator group

Description:

Pemetrexed plus cisplatin or carboplatin (based on Investigator's choice) for 4 cycles (Induction) followed by pemetrexed as single agent (Maintenance)

Treatment:

Drug: Cisplatin

Drug: Pemetrexed

Drug: Carboplatin