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

A Phase Ib, Open-label, Dose Escalation Study of LDK378 and AUY922 in Patients With ALK-rearranged Non-small Cell Lung Cancer

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer; Anaplastic Lymphoma Kinase (ALK)
• Intervention / Treatment: Drug: LDK378; Drug: AUY922

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Dept. of Anschutz Cancer (3)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Mass General
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center Fox Chase Cancer (2)
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • University of Utah / Huntsman Cancer Institute Huntsman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LDK378 and AUY922	Drug: LDK378; LDK378 is a capsule to be taken daily by mouth.; Drug: AUY922; AUY922 is an intravenous infusion that will be administered by the investigative site to the patient on a weekly basis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of Dose Limiting Toxicities (DLT)	cycle = within the first 28 days of patient's first dose	up to day 28 after the patient's first dose

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CLDK378X2102 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): January 1, 2016

Study Registration Dates

• First Submitted: January 17, 2013
• First Submitted That Met QC Criteria: January 17, 2013
• First Posted (ESTIMATE): January 21, 2013

Study Record Updates

• Last Update Posted (ACTUAL): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: anaplastic lymphoma kinase, ALK-rearranged lung cancer, non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Ceritinib
• Other Study ID Numbers: CLDK378X2102; 2012-004632-29 (EUDRACT_NUMBER)