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LDK378

Phase 2

Non-Small Cell Lung Cancer | Small molecule | Oncology |Novartis AG|Last Updated: Mar 30, 2021

Success Probability

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Trial Design

UNCONTROLLEDDMC
Total Trials3
Total Enrollment367

FDA Designations

No designations recorded

Clinical trial landscape

LDK378 · 8 trials · 7 indications

Phase 2 3Phase 1 5
NCT02450903LDK378 in Patients With ALK Positive NSCLC Previously Treated With Alectinib.Non-Small-Cell Lung Cancer
COMPLETED20 Analytics
NCT01685138LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung CancerNon-Small Cell Lung Cancer
COMPLETED124 Analytics
NCT01685060LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and CrizotinibNon-Small Cell Lung Cancer
COMPLETED140 Analytics
PHASE2COMPLETED
LDK378 in Patients With ALK Positive NSCLC Previously Treated With Alectinib.
Non-Small-Cell Lung CancerUnlock trial analytics
PHASE2COMPLETED
LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer
Non-Small Cell Lung CancerUnlock trial analytics
PHASE2COMPLETED
LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib
Non-Small Cell Lung CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Overall Response Rate (ORR) to LDK378 by Investigator Assessment
Until disease progression or unacceptable toxicity occurs, or patient withdrawal up to 798 days

ORR, defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Overall Response Rate (ORR) by Investigator Assessment
every 8 weeks (i.e. every 2 cycles; cycle = 28 days), starting from the first day of treatment with LDK378 until permanent discontinuation of study drug up to 5 years

ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed by the investigator. CR:Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Overall Response Rate (ORR) to LDK378 Per Investigator Assessment
6 cycles of 28 days up to 24 weeks

ORR per RECIST 1.1 calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf
PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose))

AUClast: The area under the concentration-time curve from time zero to the last measurable concentration time. AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours. AUCinf: Area under the plasma (serum, or blood) concentration versus time curve from time zero to infinity

Primary Pharmacokinetics (PK) Parameter of of LDK378 After Daily Oral Dose: AUC0-24h
Cycle 2 Day 1 (after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)

AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours.

Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Cmax
PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) and C2D1(after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)

Cmax is the maximum (peak) concentration of drug in plasma

Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Tmax
PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) and C2D1(after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)

Tmax is the time to reach maximum plasma concentration.

Overall Summary of Adverse Events (AEs) - Per Occurence
up to 41 months

Safety and tolerability of LDK378 at 750 mg once daily dose in Chinese adult patients with ALK-rearranged locally advanced or metastatic NSCLC

LDK378 pharmacokinetic parameters (Tmax)
18 Days

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters ( Cmax)
18 Days

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters ( AUClast)
18 Days

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters (AUCinf)
18 Days

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters (T1/2)
18 Days

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters (CL/F)
18 Days

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters (Vz/F)
18 Days

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

Incidence rate of Dose Limiting Toxicities (DLT)
up to day 28 after the patient's first dose

cycle = within the first 28 days of patient's first dose

Maximum tolerated dose (MTD) and/or Recommended dose (RD) of LDK378
During the first cycle (including the Pharmacokinetics [PK] run-in period) of LDK378 treatment. A treatment cycle consists of 21 days of daily dosing of LDK378.

As a single agent when administered orally to Japanese patients with tumors characterized by genetic alterations in ALK. The number of patients and category of Dose Limiting Toxicities (DLTs)

Number of Participants With Dose Limiting Toxicities (DLTs)
33 months

The maximum tolerated dose (MTD) was defined as the highest dose for a given schedule that was expected to cause DLTs in no more than 33% of patients during the first cycle of treatment. A patient with multiple occurrences of a DLT under one treatment is counted only once in the AE category for that treatment. MTD was determined at 750mg.

Secondary Endpoints

Disease Control Rate (DCR)
6 cycles of 28 days up to 798 days
Time to Tumor Response (TTR)
6 cycles of 28 days up to 798 days
Duration of Response (DOR)
6 cycles of 28 days up to 798 days
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
LDK378 (Ceritinib)EXPERIMENTALParticipants who received LDK378 750mg once daily on a 28 day cycle.
LDK378EXPERIMENTALPatients treated with ceritinib/LDK378 750 mg once-daily, fasted
Normal Hepatic FunctionEXPERIMENTALSubjects with normal hepatic function
Mild Hepatic ImpairmentEXPERIMENTALSubjects with mild hepatic impairment
Moderate Hepatic ImpairmentEXPERIMENTALSubjects with moderate hepatic impairment
Severe Hepatic ImpairmentEXPERIMENTALSubjects with severe hepatic impairment
LDK378 and AUY922EXPERIMENTAL -
Dose-escalationEXPERIMENTALOpen-label dose escalation study of LDK378, administered orally in Japanese patients with tumors characterized by genetic alterations in anaplastic lymphoma kinase (ALK)
Dose-expansionEXPERIMENTALOpen-label study of LDK378, administered orally in Japanese patients with tumors characterized by genetic alterations in ALK to see further safety, anti-tumor activity, and PK data in patients who has progressed since prior therapy with alectinib
LDK378 750 mg: Arm 1A and Arm 1BEXPERIMENTALNSCLC patients previously treated with an ALK inhibitor
LDK378 750 mg: Arm 2EXPERIMENTALNSCLC patients not previously treated with an ALK inhibitor
LDK378 750 mg: Arm 3EXPERIMENTALPatients with other tumors that are ALK positive other than NSCLC

Interventions

NameTypeDescription
LDK378DRUGOral LDK378 750mg once daily
AUY922DRUGAUY922 is an intravenous infusion that will be administered by the investigative site to the patient on a weekly basis.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites9

Key Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of Stage IIIb or IV NSCLC that carries an ALK rearrangement as determined locally by Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test. * Patients must have NSCLC that has progressed at study enrollment. *...

Countries:JapanUnited StatesAustraliaBelgiumCanadaFranceHong KongItalyNew ZealandNorwayRussiaSingaporeSouth KoreaSpainSwedenTaiwanThailandUnited KingdomGermanyNetherlandsChina
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Competitive Landscape -Non-Small Cell Lung Cancer 389 trials

Frequently asked questions about LDK378

What is LDK378 used for?

LDK378 is an investigational small molecule being studied for the treatment of tumors characterized by genetic alterations in anaplastic lymphoma kinase (ALK), including non-small-cell lung cancer (NSCLC). It is being developed by Novartis AG (NVS) and is currently in clinical trials, though it is not yet approved.

What does LDK378 target?

LDK378 targets the anaplastic lymphoma kinase (ALK) protein. It is designed to treat cancers, particularly non-small-cell lung cancer, that have genetic alterations or abnormalities in ALK. The drug is being studied in patients whose tumors harbor these specific genetic changes.

Who makes LDK378?

LDK378 is being developed by Novartis AG, a global pharmaceutical company traded on the New York Stock Exchange under the ticker symbol NVS. Novartis is conducting clinical trials to evaluate the safety and efficacy of LDK378 in patients with ALK-altered tumors.

What phase is LDK378 in?

LDK378 is in Phase 1 and Phase 2 clinical trials. The drug is investigational and has not been approved by regulatory authorities. It is being studied in early-stage trials to assess dosing, safety, and preliminary efficacy in patients with ALK-positive tumors.

What clinical trials is LDK378 in?

LDK378 has been studied in several completed clinical trials, including NCT01283516, a Phase 1 dose escalation/expansion study in patients with ALK genetic abnormalities; NCT01772797, a Phase 1b study combining LDK378 with AUY922 in ALK-rearranged NSCLC; and NCT01950481, a pharmacokinetic study in hepatic impairment.

Is LDK378 the same as ceritinib?

LDK378 is also known as ceritinib, an ALK inhibitor developed by Novartis. While the data provided does not explicitly state this alternative name, LDK378 is the investigational code for the drug that is commonly referred to as ceritinib in medical literature.