Clinical trial NCT02276027: 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
Official title: A Phase II, Open Label, Multiple Arm Study of Single Agent AUY922, BYL719, INC280, LDK378 and MEK162 in Chinese Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma
Keywords: adenocarcinoma lung cancer,
squamous cell lung carcinoma,
NSCLC
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-10-27
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 231 weeks
Secondary outcomes:
measure: Median Overall Survival (OS)
timeFrame: Up to 231 weeks
measure: Number of Participants With Progression-free Survival (PFS)
timeFrame: Up to 231 weeks
measure: Disease Control Rate (DCR)
timeFrame: Up to 231 weeks
measure: Median Duration of Overall Response (DOR)
timeFrame: Up to 231 weeks
measure: Number of Participants With Adverse Events
timeFrame: up to 235 weeks
measure: Pharmacokinetics Profile, AUCtau and AUClast
timeFrame: Day 1 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours) and Day 15 (pre dose, 0.5, 1, 2, 4, 6, 8 hours post dose and only for BYL719 350 mg QD and LDK378 750 mg QD arms also at 24 hours post dose)
measure: Pharmacokinetics Profile, Cmax
timeFrame: Day 1 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours) and Day 15 (pre dose, 0.5, 1, 2, 4, 6, 8 hours post dose and only for BYL719 350 mg QD and LDK378 750 mg QD arms also at 24 hours post dose)
measure: Pharmacokinetics Profile, Tmax
timeFrame: Day 1 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours) and Day 15 (pre dose, 0.5, 1, 2, 4, 6, 8 hours post dose and only for BYL719 350 mg QD and LDK378 750 mg QD arms also at 24 hours post dose)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: