A Phase II, Open Label, Multiple Arm Study of AUY922, BYL719, INC280, LDK378 and MEK162 in Chinese Patients With Advanced Non-small Cell Lung Cancer

NCT ID: NCT02276027

Last Updated: 2020-12-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-20
• Study Completion Date: 2019-10-15

Brief Summary

The purpose of this study was to evaluate the anti-tumor activity of single agent BYL719, INC280, LDK378 and MEK162 in advanced NSCLC patients carrying specific molecular alterations.

There is a great unmet medical need in NSCLC patients with advanced or metastatic disease. Novel approaches using targeted therapeutic agents for these patient populations with molecular characterization could potentially identify subsets of advanced NSCLC patients who would benefit from targeted kinase inhibition. Study treatments, BYL719, INC280, LDK378 and MEK162, which target PIK3CA, c-MET, ALK/ROS1 and MEK respectively, have shown promising data in either preclinical or clinical lung cancer settings.

Detailed Description

To enter the screening phase of the study, the subjects' molecular alterations were determined using locally validated methodologies from a newly obtained tumor sample (preferred) or the most recent archival tumor sample available. Based on the molecular alterations of the tumor, subjects were assigned to one of the treatment arms. Subjects with multiple molecular alterations in epidermal growth factor receptor (EGFR) and the relevant pathways were excluded, except under the conditions described in Inclusion criteria.

The treatment period began on Cycle 1 Day 1 and continued in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of informed consent, death or the subject transferred to another Novartis study that could continue to provide the study drug.

All subjects were required to be followed up for 30 days for safety after receiving the last dose of study treatment. Subjects who discontinued study treatment for any reason other than disease progression were followed up for progression of disease. All subjects were required to be followed for survival. For subjects transferred to another Novartis study, an end of treatment visit (EOT) was required to be performed and the subject would not enter the follow-up period.

Conditions

Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma

Keywords

adenocarcinoma lung cancer,; squamous cell lung carcinoma,; NSCLC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BYL719 350 mg QD

Patient's tumor must have molecular alteration of the PIK3CA gene.

Group Type: EXPERIMENTAL

BYL719

Intervention Type: DRUG

BYL719 was dosed as 350 mg once daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to take BYL719 exactly as prescribed.

INC280 400 mg BID tab/600 mg BID cap

Patient's tumor must have molecular alteration of the c-MET gene.

Group Type: EXPERIMENTAL

INC280

Intervention Type: DRUG

INC280 was dosed as 600 mg (tablet) or 400mg(Capsule) twice daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to takeINC280 exactly as prescribed.

LDK378 750 mg QD

Patient's tumor must have ALK or ROS1 gene rearrangement.

Group Type: EXPERIMENTAL

LDK378

Intervention Type: DRUG

LDK378 was dosed as 750 mg once daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to take LDK378 exactly as prescribed.

MEK162 45 mg BID

Patient's tumor must have KRAS, NRAS or BRAF mutation.

Group Type: EXPERIMENTAL

MEK162

Intervention Type: DRUG

MEK162 was dosed as 45 mg twice daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to take MEK162 exactly as prescribed.

Interventions

BYL719

BYL719 was dosed as 350 mg once daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to take BYL719 exactly as prescribed.

Intervention Type: DRUG

INC280

INC280 was dosed as 600 mg (tablet) or 400mg(Capsule) twice daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to takeINC280 exactly as prescribed.

Intervention Type: DRUG

LDK378

LDK378 was dosed as 750 mg once daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to take LDK378 exactly as prescribed.

Intervention Type: DRUG

MEK162

MEK162 was dosed as 45 mg twice daily. On the first day of each cycle, patient received a prescription of adequate drug supply for self-administration at home. The investigator must emphasized compliance and instructed the patient to take MEK162 exactly as prescribed.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Advanced (stage IIIB or stage IV) NSCLC
• Must have specific molecular alterations

Exclusion Criteria

• Symptomatic central nervous system (CNS) metastases which are neurologically unstable or requiring increasing doses of steroids within the 4 weeks prior to study entry to control their CNS disease
• Radiation therapy within ≤ 4 weeks prior to study entry, with the exception of limited field palliative radiotherapy for bone pain relief.
• Any other malignancies within the last 5 years before study entry
• Major surgery ≤ 2 weeks prior to study entry or who have not recovered from side effects of such therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Guangzhou, Guangdong, China

Countries

China

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CINC280X2205

Identifier Type: -

Identifier Source: org_study_id