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

Novartis

Status and phase: Completed; Phase 2

Conditions: Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma

Treatments: Drug: LDK378; Drug: BYL719; Drug: MEK162; Drug: INC280

Study type: Interventional

Funder types: Industry

Identifiers

NCT02276027

CINC280X2205

Details and patient eligibility

About

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.

Full 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.

Enrollment: 66 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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66 participants in 4 patient groups

BYL719 350 mg QD

Experimental group

Description:

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

Treatment:

Drug: BYL719

INC280 400 mg BID tab/600 mg BID cap

Experimental group

Description:

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

Treatment:

Drug: INC280

LDK378 750 mg QD

Experimental group

Description:

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

Treatment:

Drug: LDK378

MEK162 45 mg BID

Experimental group

Description:

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

Treatment:

Drug: MEK162