Phase Ib Study of LDK378 and AUY922 in ALK-rearranged Non-small Cell Lung Cancer

Phase 1

Completed

• Conditions: Non-small Cell Lung Cancer; Anaplastic Lymphoma Kinase (ALK)
• Interventions: Drug: LDK378; Drug: AUY922

• Registration Number: NCT01772797
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The primary purpose of the study is to estimate the maximum tolerated dose of the combination of LDK378 and AUY922. This study will assess the safety, tolerability, pharmacokinetics and preliminary evidence of anti-tumor activity of the combination of LDK378 and AUY922 in ALK-rearranged non-small cell lung cancer.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-01-17
• Study First Submitted QC: 2013-01-17
• Study First Posted: 2013-01-21
• Study Start: 2013-06
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2016-09
• Last Update Submitted: 2020-12-16
• Last Update Posted: 2020-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• locally advanced or metastatic NSCLC that has progressed during or following therapy with an ALK inhibitor
• tumor must carry an ALK rearrangement in 15% or more of tumor cells as measured by FISH
• disease that can be evaluated by RECIST v1.1 and measurable disease

Exclusion Criteria

• central nervous system (CNS) metastases that are symptomatic or require increasing steroids or CNS-directed therapy to control CNS disease
• history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis
• clinically significant cardiac dysfunction
• inadequate end organ function as defined by specified laboratory values
• use of medications known to be strong inhibitors or inducters of CYP3A4/5 that cannot be discontinued at least 1 week prior to start of treatment
• use of medications that are mainly metabolized by CYP3A4/5 or CYP2C9 that cannot be discontinued at least 1 week prior to start of treatment
• clinically significant, uncontrolled impaired gastrointestinal function or GI disease
• prior treatment with a HSP90 inhibitor
• radiotherapy to lung within 4 weeks prior to the first dose of study treatment or patients who have not recovered from radiotherapy-related toxicities
• pregnant or nursing women
• history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LDK378 and AUY922	LDK378	-
LDK378 and AUY922	AUY922	-

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	30 months	Assess the anti-tumor activity of LDK378 and AUY922
Plasma PK parameter of LDK378 and AUY922: Cmax	30 months	Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Plasma PK parameter of LDK378 and AUY922: AUCtau	30 months	Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Number of patients with adverse events	30 months	Characterize the safety and tolerability of LDK378 and AUY922 in patients
Assessments of dose interruptions, reductions, and dose intensity	30 months	Characterize the safety and tolerability of LDK378 and AUY922 in patients
Duration of Response (DoR)	30 months	Assess the anti-tumor activity of LDK378 and AUY922
Plasma PK parameter of LDK378 and AUY922: AUClast	30 months	Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Plasma PK parameter of LDK378 and AUY922: Racc	30 months	Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Changes in laboratory values	30 months	Characterize the safety and tolerability of LDK378 and AUY922 in patients
Assessments of electrocardiograms	30 months	Characterize the safety and tolerability of LDK378 and AUY922 in patients
Time to Response (TTR)	30 months	Assess the anti-tumor activity of LDK378 and AUY922
Plasma PK parameter of LDK378 and AUY922: Tmax	30 months	Characterize single and multiple dose PK of LDK378 and AUY922 in patients
Progression free survival (PFS)	30 months	Assess the anti-tumor activity of LDK378 and AUY922 per RECIST 1.1
Number of patients with serious adverse events	30 months	Characterize the safety and tolerability of LDK378 and AUY922 in patients
Plasma PK parameter of LDK378 and AUY922: Cmin	30 months	Characterize single and multiple dose PK of LDK378 and AUY922 in patients

Trial Locations

Locations (5)

Massachusetts General Hospital Mass General; 🇺🇸 Boston, Massachusetts, United States

Fox Chase Cancer Center Fox Chase Cancer (2); 🇺🇸 Philadelphia, Pennsylvania, United States

Novartis Investigative Site; 🇪🇸 Barcelona, Catalunya, Spain

University of Utah / Huntsman Cancer Institute Huntsman; 🇺🇸 Salt Lake City, Utah, United States

University of Colorado Dept. of Anschutz Cancer (3); 🇺🇸 Aurora, Colorado, United States