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OpenTrials
Completed

NCT Number: 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

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.

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Key information

Conditions

Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma Adenocarcinoma Adenocarcinoma of Lung Carcinoma Lung Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site

Guangzhou, Guangdong, 51000, China

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BYL719

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

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

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

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.

Primary outcomes

  1. Overall Response Rate (ORR)

    Time frame: Up to 231 weeks

    Overall response rate is the proportion of patients with a best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria (Overall Response (OR) = CR + PR).

    Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Secondary outcomes

  1. Median Overall Survival (OS)

    Time frame: Up to 231 weeks

    OS is defined as the time from date of randomization/start of treatment to date of death due to any cause.

  2. Number of Participants With Progression-free Survival (PFS)

    Time frame: Up to 231 weeks

    PFS event is defined as the first documented progression or death due to any cause according to RECIST 1.1 criteria

  3. Disease Control Rate (DCR)

    Time frame: Up to 231 weeks

    DCR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR) or Stable Disease (SD) according to RECIST 1.1 criteria (DCR: CR+PR+SD) Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD

  4. Median Duration of Overall Response (DOR)

    Time frame: Up to 231 weeks

    Duration of overall response (DOR) is defined as the time from the first documented CR or PR (confirmed by the subsequent assessment) to the date of the first documented progression or death due to underlying cancer.

  5. Number of Participants With Adverse Events

    Time frame: up to 235 weeks

    Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

    If CTCAE grading does not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to grades 1 - 4, was used.

  6. Pharmacokinetics Profile, AUCtau and AUClast

    Time frame: 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)

    PK parameters are estimated from each individual plasma concentration-time profile using non-compartmental analysis (Phoenix software version 6.2 and above).

    AUCtau is the AUC calculated to the end of a dosing interval (tau) (amount x time x volume-1) AUClast is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) On Cycle 1 Day 1, PK parameters for only BYL719 350 mg QD arm were analyzed

  7. Pharmacokinetics Profile, Cmax

    Time frame: 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)

    PK parameters are estimated from each individual plasma concentration-time profile using non-compartmental analysis (Phoenix software version 6.2 and above).

    Cmax is the maximum (peak) observed plasma concentration (mass x volume-1) On Cycle 1 Day 1, PK parameters for only BYL719 350 mg QD arm were analyzed

  8. Pharmacokinetics Profile, Tmax

    Time frame: 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)

    PK parameters are estimated from each individual plasma concentration-time profile using non-compartmental analysis (Phoenix software version 6.2 and above).

    Tmax is the time to reach maximum (peak) plasma concentration (time) On Cycle 1 Day 1, PK parameters for only BYL719 350 mg QD arm were analyzed

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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)

Important dates

Study start
2015
Primary completion
2019
Study completion
2019
First posted
Oct 27, 2014
Registry last updated
Dec 16, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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