Adenocarcinoma Lung Cancer; Squamous Cell Lung CarcinomaPhase 2NCT02276027
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
A Phase 2 study testing BYL719, INC280 and LDK378 in people with Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma, run by Novartis Pharmaceuticals at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma
- What is being tested?
- BYL719, INC280 and LDK378
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteChina
- Study dates
- 20 Jan 2015to 15 Oct 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced (stage IIIB or stage IV) NSCLC
- Must have specific molecular alterations
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Being tested
- BYL719, INC280, LDK378, MEK162
- Keywords
- adenocarcinoma lung cancer,, squamous cell lung carcinoma,, NSCLC
- Medical subject headings
- Adenocarcinoma of Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BYL719Drug
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.
INC280Drug
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.
LDK378Drug
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.
MEK162Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| BYL719 350 mg QD | Experimental | Patient's tumor must have molecular alteration of the PIK3CA gene. Receives: Drug: BYL719 |
| INC280 400 mg BID tab/600 mg BID cap | Experimental | Patient's tumor must have molecular alteration of the c-MET gene. Receives: Drug: INC280 |
| LDK378 750 mg QD | Experimental | Patient's tumor must have ALK or ROS1 gene rearrangement. Receives: Drug: LDK378 |
| MEK162 45 mg BID | Experimental | Patient's tumor must have KRAS, NRAS or BRAF mutation. Receives: Drug: MEK162 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
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.
Measured: Up to 231 weeks
Secondary outcomes (8)
Median Overall Survival (OS)
OS is defined as the time from date of randomization/start of treatment to date of death due to any cause.
Measured: Up to 231 weeks
Number of Participants With Progression-free Survival (PFS)
PFS event is defined as the first documented progression or death due to any cause according to RECIST 1.1 criteria
Measured: Up to 231 weeks
Disease Control Rate (DCR)
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
Measured: Up to 231 weeks
Median Duration of Overall Response (DOR)
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.
Measured: Up to 231 weeks
Number of Participants With Adverse Events
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.
Measured: up to 235 weeks
Pharmacokinetics Profile, AUCtau and AUClast
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
Measured: 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)
Pharmacokinetics Profile, Cmax
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
Measured: 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)
Pharmacokinetics Profile, Tmax
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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2014 (estimated)
- Study start20 Jan 2015
- Primary completion15 Oct 2019
- Study completion15 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adenocarcinoma Lung Cancer; Squamous Cell Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02276027
- Sponsor's protocol ID
- CINC280X2205
- Status last verified
- Nov 2020
- First submitted
- 9 Oct 2014
- Last updated
- 16 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02276027
- Acronym / sponsor ID
- CINC280X2205
- Keywords
- adenocarcinoma lung cancer,, squamous cell lung carcinoma,, NSCLC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Jan 2015 (actual)
- Primary completion
- 15 Oct 2019 (actual)
- Study completion
- 15 Oct 2019 (actual)
- First posted
- 27 Oct 2014 (estimated)
- Results
- Posted 16 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| BYL719 350 mg QD | Experimental | Drug: BYL719Patient's tumor must have molecular alteration of the PIK3CA gene. |
| INC280 400 mg BID tab/600 mg BID cap | Experimental | Drug: INC280Patient's tumor must have molecular alteration of the c-MET gene. |
| LDK378 750 mg QD | Experimental | Drug: LDK378Patient's tumor must have ALK or ROS1 gene rearrangement. |
| MEK162 45 mg BID | Experimental | Drug: MEK162Patient's tumor must have KRAS, NRAS or BRAF mutation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Advanced (stage IIIB or stage IV) NSCLC
- Must have specific molecular alterations
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BYL719BYL719 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. | Drug | BYL719 350 mg QD |
| INC280INC280 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. | Drug | INC280 400 mg BID tab/600 mg BID cap |
| LDK378LDK378 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. | Drug | LDK378 750 mg QD |
| MEK162MEK162 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. | Drug | MEK162 45 mg BID |
Primary outcome
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.
8 secondary outcomes
Median Overall Survival (OS)
Time frame: Up to 231 weeks
Number of Participants With Progression-free Survival (PFS)
Time frame: Up to 231 weeks
Disease Control Rate (DCR)
Time frame: Up to 231 weeks
Median Duration of Overall Response (DOR)
Time frame: Up to 231 weeks
Number of Participants With Adverse Events
Time frame: up to 235 weeks
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)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BYL719, INC280 and LDK378 in people with Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma, run by Novartis Pharmaceuticals at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: Up to 231 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2020.