LDK378 in Patients With ALK Positive NSCLC Previously Treated With Alectinib.

A Phase II, Multi-center, Open-label, Single-Arm Study to Evaluate the Efficacy and Safety of Oral LDK378 Treatment for Patients With ALK-Positive Non-Small Cell Lung Cancer Previously Treated With Alectinib

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02450903

Enrollment

Registered

2015-05-21

Start date

2015-08-21

Completion date

2018-05-24

Last updated

2021-03-30

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

Keywords

Non-Small-Cell Lung Cancer, NSCLC, ALK, LDK378, alectinib, Non-small cell lung carcinoma (NSCLC), lung cancer, lung adenocarcinoma, Non small cell lung carcinoma, Non small cell lung cancer, Non-small cell lung cancer

Brief summary

This was a single-arm, open-label, multicenter, phase II study to evaluate the efficacy and safety of the ALK inhibitor LDK378 when used as single agent in patients with ALK-rearranged stage IIIB or IV NSCLC previously treated with alectinib. Treatment with LDK378 750 mg qd continued until the patient experienced disease progression as determined by the investigator according to RECIST 1.1, unacceptable toxicity that precluded further treatment, pregnancy, start of a new anticancer therapy, discontinued treatment at the discretion of the patient or investigator, lost to follow-up, death, or study was terminated by Sponsor.

Detailed description

Study completed as per protocol. 'Switched to commercial drug' implies that after the primary and secondary objectives were achieved, one patient continued the study treatment as they did not meet the progression disease or AE to be discontinued from the treatment. But after the regulatory approval, Novartis decided to close the study, the 1 patient switched to commercially available drug.

Interventions

DRUGLDK378

Oral LDK378 750mg once daily

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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. * Patients must have received previous treatment with alectinib for treatment of locally advanced or metastatic NSCLC. Prior therapy with crizotinib as ALK inhibitor therapy in addition to alectinib is allowed. Alectinib doesn't need to be the last therapy prior to study enrollment. No particular sequence of prior alectinib and crizotinib is required for enrollment. * Patients must be chemotherapy-naïve or have received only one line of prior cytotoxic chemotherapy. * Age 18 years or older at the time of informed consent. Key

Exclusion criteria

* Patients with known hypersensitivity to any of the excipients of LDK378. * Prior therapy with other ALK inhibitor investigational agents except crizotinib and alectinib. * Prior systemic anti-cancer (including investigational) therapy aside from alectinib, crizotinib and one regimen of previous cytotoxic chemotherapy for locally advanced or metastatic NSCLC. * Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms. * Patient with history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis. * Patients with history of carcinomatous meningitis. * Patient with a concurrent malignancy or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. * Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months)

Design outcomes

Primary

Measure	Time frame	Description
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.

Secondary

Measure	Time frame	Description
Time to Tumor Response (TTR)	6 cycles of 28 days up to 798 days	TTR, calculated as the time from first dose of LDK378 to first documented response (CR or PR) evaluated by investigator per RECIST 1.1 for participants with confirmed PR or CR.
Duration of Response (DOR)	6 cycles of 28 days up to 798 days	DOR, calculated as the time from the date of the first documented response (CR or PR) to the first documented disease progression evaluated by investigator per RECIST 1.1 or death due to any cause
Disease Control Rate (DCR)	6 cycles of 28 days up to 798 days	DCR, calculated as the percentage of participants with best overall response of CR, PR, or stable disease (SD) evaluated by investigator per RECIST 1.1; 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; SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD); PD: taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Overall Survival (OS)	6 cycles of 28 days up to 798 days	OS was defined as the time from the start date of study drug to the date of death due to any cause.
Overall Intracranial Response Rate (OIRR)	6 cycles of 28 days up to 798 days	OIRR, calculated as the percentage of participants with a best overall confirmed response of CR or PR in the brain assessments for participants having measurable brain metastases at baseline
Progression Free Survival (PFS)	6 cycles of 28 days up to 798 days	PFS, calculated as the time from first dose of LDK378 to date of first documented disease progression evaluated by investigator per RECIST 1.1 or date of death due to any cause

Countries

Japan

Participant flow

Recruitment details

Approximately 20 patients were planned to be enrolled.

Pre-assignment details

A total of 20 patients were enrolled and treated with ceritinib.

Participants by arm

Arm	Count
LDK378 (Ceritinib) Participants who received LDK378 750mg once daily on a 28 day cycle.	20
Total	20

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	3
Overall Study	Progressive disease	15
Overall Study	Subject/guardian decision	1
Overall Study	Switched to commercial drug	1

Baseline characteristics

Characteristic	LDK378 (Ceritinib)
Age, Continuous	52.2 Years STANDARD_DEVIATION 15.88
Race/Ethnicity, Customized Japanese	19 Participants
Race/Ethnicity, Customized Other	1 Participants
Sex: Female, Male Female	12 Participants
Sex: Female, Male Male	8 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 20
other Total, other adverse events	20 / 20
serious Total, serious adverse events	9 / 20

Outcome results

Primary

Overall Response Rate (ORR) to LDK378 by Investigator Assessment

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.

Time frame: Until disease progression or unacceptable toxicity occurs, or patient withdrawal up to 798 days

Population: Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.

Arm	Measure	Value (NUMBER)
LDK378 (Ceritinib)	Overall Response Rate (ORR) to LDK378 by Investigator Assessment	25.0 Percentage of participants

Secondary

Disease Control Rate (DCR)

DCR, calculated as the percentage of participants with best overall response of CR, PR, or stable disease (SD) evaluated by investigator per RECIST 1.1; 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; SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD); PD: taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.