A Dose Escalation/Expansion Study of LDK378 in Patients With Tumors Characterized by Genetic Abnormalities in Anaplastic Lymphoma Kinase

Novartis

Status and phase: Completed; Phase 1

Conditions: Tumors Characterized by Genetic Abnormalities of ALK

Treatments: Drug: LDK378

Study type: Interventional

Funder types: Industry

Identifiers

NCT01283516

CLDK378X2101

2010-019827-70 (EudraCT Number)

Details and patient eligibility

About

This study assessed the safety and efficacy of LDK378 in adult patients with genetic abnormalities in anaplastic lymphoma kinase (ALK).

Enrollment: 304 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ECOG Performance Status of ≤ 2 and life expectancy of ≥ 12 weeks.
• Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists. Only patients with tumors characterized by genetic abnormalities in ALK were enrolled.
• For NSCLC, an ALK translocation must be detected by FISH in ≥ 15% of tumor cells.
• In patients with diseases other than NSCLC, ALK translocation is not required and overexpression of ALK protein may be considered indicative of a genetic abnormality in ALK.
• Patients with measurable or non-measurable disease as determined by modified RECIST version 1.0 in dose-escalation phase, and patients with at least one measurable lesion as determined by RECIST 1.0 in expansion phase.

Exclusion criteria

• Patients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or required increasing doses of steroids to control their CNS disease were excluded.
• Patients with a prior or current history of a second malignancy, impaired GI function, history of pancreatitis or increased amylase or lipase, known diagnosis of HIV, and clinically significant cardiac disease were excluded.
• Patients treated with chemotherapy or biologic therapy or other investigational agent < 2 weeks prior to starting study drug for compounds with a half-life ≤ 3 days, and < 4 weeks prior to starting study drug for compounds with a prolonged half-life were excluded.
• Further, patients treated with medications that were known to be strong inhibitors or inducers of CYP3A4/5 that could not be discontinued at least a week prior to start of treatment with LDK378 and for the duration of the study were also excluded.

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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304 participants in 3 patient groups

LDK378 750 mg: Arm 1A and Arm 1B

Experimental group

Description:

NSCLC patients previously treated with an ALK inhibitor

Treatment:

Drug: LDK378

LDK378 750 mg: Arm 2

Experimental group

Description:

NSCLC patients not previously treated with an ALK inhibitor

Treatment:

Drug: LDK378

LDK378 750 mg: Arm 3

Experimental group

Description:

Patients with other tumors that are ALK positive other than NSCLC

Treatment:

Drug: LDK378