LDK378 versus chemotherapy in previously untreated patients with ALK rearranged non-small cell lung cancer

A phase III multicenter, randomized study of oral LDK378 versus standard chemotherapy in previously untreated adult patients with ALK rearranged (ALK-positive), stage IIIB or IV, non-squamous non-small cell lung cancer

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2013-000319-26-AT

Enrollment

348

Registered

2013-05-22

Start date

2013-07-17

Completion date

Unknown

Last updated

2024-04-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

non-small cell lung cancer (NSCLC) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Interventions

Trade Name: Zykadia Product Code: LDK378 Pharmaceutical Form: Capsule, hard Other descriptive name: LDK378 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150- Tra

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Patient has a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that is Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test will be performed at Novartis designated central laboratories. 2. Patient has newly diagnosed stage IIIB (who are 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 exception of neo-adjuvant or adjuvant therapy. 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. Other protocol-defined inclusion criteria may apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 210 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 138

Exclusion criteria

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 platinum containing drugs, pemetrexed or any known excipients of these drugs. 3. Patient with symptomatic central nerous 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. Other protocol-defined exclusion criteria may apply

Design outcomes

Primary

Measure	Time frame
Main Objective: To compare the antitumor activity of LDK378 versus reference chemotherapy, as measured by PFS determined by a BIRC;Secondary Objective: Key secondary: - To compare OS in patients treated with LDK378 versus reference chemotherapy Other secondary: 1. To assess the antitumor activity of LDK378 versus reference chemotherapy, as measured by ORR, DOR, DCR, and TTR determined by BIRC and by investigators 2. To assess the antitumor activity of LDK378 versus reference chemotherapy, as measured by PFS determined by investigators 3. To assess the antitumor activity of LDK378 versus reference chemotherapy in the brain, as measured by OIRR, IDCR and DOIR as determined by BIRC neuroradiologist per modified RECIST 1.1 4. To assess the effect of LDK378 versus reference chemotherapy on PROs, including disease related symptoms, functioning, and health-related quality of life 5. To characterize the PK of LDK378 in this patient population ;Primary end point(s): progression free survival (PFS), defined as time from date of randomization to date of first documented disease progression (as assessed by BIRC per RECIST 1.1) or date of death due to any cause;Timepoint(s) of evaluation of this end point: Month 33	—

Measure

Time frame

Main Objective: To compare the antitumor activity of LDK378 versus reference chemotherapy, as measured by PFS determined by a BIRC;Secondary Objective: Key secondary: - To compare OS in patients treated with LDK378 versus reference chemotherapy Other secondary: 1. To assess the antitumor activity of LDK378 versus reference chemotherapy, as measured by ORR, DOR, DCR, and TTR determined by BIRC and by investigators 2. To assess the antitumor activity of LDK378 versus reference chemotherapy, as measured by PFS determined by investigators 3. To assess the antitumor activity of LDK378 versus reference chemotherapy in the brain, as measured by OIRR, IDCR and DOIR as determined by BIRC neuroradiologist per modified RECIST 1.1 4. To assess the effect of LDK378 versus reference chemotherapy on PROs, including disease related symptoms, functioning, and health-related quality of life 5. To characterize the PK of LDK378 in this patient population ;Primary end point(s): progression free survival (PFS), defined as time from date of randomization to date of first documented disease progression (as assessed by BIRC per RECIST 1.1) or date of death due to any cause;Timepoint(s) of evaluation of this end point: Month 33

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Secondary

Measure	Time frame
Secondary end point(s): key secondary: - overall survival (OS), defined as time from date of randomization to date of death due to any cause other secondary: The following endpoints will be evaluated by BIRC and by investigator assessment per RECIST 1.1: – ORR, defined as the proportion of patients with a best overall response defined as CR or PR; (CR+PR) – DOR, defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause – DCR, defined as the proportion of patients with best overall response of CR, PR, or SD – TTR, defined as the time from date of randomization to date of first documented response (CR or PR) Other secondary endpoints as per full protocol may apply;Timepoint(s) of evaluation of this end point: for key secondary: Month 33 for other secondary: Month 33	—

Measure

Time frame

Secondary end point(s): key secondary: - overall survival (OS), defined as time from date of randomization to date of death due to any cause other secondary: The following endpoints will be evaluated by BIRC and by investigator assessment per RECIST 1.1: – ORR, defined as the proportion of patients with a best overall response defined as CR or PR; (CR+PR) – DOR, defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause – DCR, defined as the proportion of patients with best overall response of CR, PR, or SD – TTR, defined as the time from date of randomization to date of first documented response (CR or PR) Other secondary endpoints as per full protocol may apply;Timepoint(s) of evaluation of this end point: for key secondary: Month 33 for other secondary: Month 33

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Countries

Argentina, Australia, Austria, Brazil, China, Colombia, Denmark, France, Germany, Greece, Hungary, India, Ireland, Italy, Japan, Korea, Republic of, Lebanon, Mexico, Netherlands, Norway, Poland, Portugal, Russian Federation, Singapore, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom

Contacts

Public ContactDrug regulatory Affairs

Novartis Pharma GmbH

austria.dra@novartis.com+43 1 866570

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026