Non Small Cell Lung CancerPhase 2NCT02323126
Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer
A Phase 2 study testing EGF816, INC280 and Nivolumab in people with Non Small Cell Lung Cancer, run by Novartis Pharmaceuticals at 13 sites in 8 countries.
Trial summary
To determine the efficacy and safety of nivolumab in combination with EGF816 and of nivolumab in combination with INC280 in previously treated NSCLC patients Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- EGF816, INC280 and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 13 sitesin 8 countries
- Study dates
- 9 Feb 2015to 5 Feb 2021
- 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
- Written informed consent must be obtained prior to any screening procedures
- Presence of at least one measurable lesion according to RECIST v.1.1
- ECOG performance status ≤ 2
- Patients with histologically documented locally advanced, recurrent and/or metastatic NSCLC
- Tumor tissue for determination and/or confirmation of genetic pre-requisites (i.e. EGFR T790M positivity post progression on EGFR TKI for Group 1; cMet status for Group 2) must be provided for analysis
- Group 1 patients:
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- Patients with EGFR T790M NSCLC (adenocarcinoma)
- Documented progression of disease according to RECIST v1.1 following primary standard of care (e.g. erlotinib, gefitinib)
- Group 2 patients:
- Patients with EGFR wild-type NSCLC
- Documented progression of disease according to RECIST v1.1 following standard of care (e.g. platinum doublet).
Who cannot join
- Patients who have received more than one prior line of EGFR TKI therapy1 (applies only to Group 1)
- Previous treatment with a c-MET inhibitor or HGF-targeting therapy (applies only to Group 2)
- Patients with brain metastases. However, if radiation therapy and/or surgery has been completed and serial evaluation by CT (with contrast enhancement) or MRI over a minimum of one month demonstrates the disease to be stable and if the patient remains asymptomatic without the need for treatment with steroids
- Patients who require emergent use of systemic steroids, chronic use of prednisone (greater than 10mg or an equivalent steroid dose daily) or emergent surgery and/or radiotherapy.
- History of allergy or hypersensitivity to nivolumab components
- Patients with any known or suspected, current or past history of, autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
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- Patients with a condition requiring chronic systemic treatment with either corticosteroids(> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of treatment start. Inhaled or topical steroids, and adrenal replacement steroid doses> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
- Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
- Patients who have been treated with prior PD-1 and PD-L1 agents
- Patients who previously received agents targeting c-MET and/or EGFR T790M Note: Previous treatment with afatinib may be allowable after discussions between Novartis and Investigator.
- Patients with the following laboratory abnormalities:
- Absolute Neutrophil Count (ANC) <1.5 x 109/L
- Hemoglobin (Hgb) <9 g/dL
- Platelets <100 x 109/L
- Total bilirubin >1.5 x upper limit of normal (ULN). For patients with Gilbert's syndrome total bilirubin >2.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN
- Serum creatinine >1.5 x ULN and/or measured or calculated creatinine clearance <75% LLN
- For patients being screened for Group 2, asymptomatic serum amylase > CTCAE Grade 2 (1.5-2.0 x ULN). Patients with Grade 1 or Grade 2 serum amylase at the beginning of the study must be confirmed to have no signs or symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.)
- For patients being screened for Group 2: Serum lipase > ULN
- Female patients who are either pregnant or nursing.
- Women of child bearing potential who refuse or are not able to use a highly effective method of contraception as defined in the study protocol.
- Sexually active males unless they use a condom during intercourse while taking drug and for 31 weeks after the last dose of study treatment.
Trial locations and contacts
13 sites in 8 countries.
13 sites in 8 countries
Spain4 sites
Novartis Investigative Site
Alicante, Valencia, 03010
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28040
Novartis Investigative Site
Málaga, Andalusia, 29010
Australia2 sites
Novartis Investigative Site
Camperdown, New South Wales, 2050
Novartis Investigative Site
Chermside, Queensland, 4032
Italy2 sites
Novartis Investigative Site
Aviano, PN, 33081
Novartis Investigative Site
Perugia, PG, 06129
United States1 site
University of Texas MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2)
Houston, Texas, 77030
Germany1 site
Novartis Investigative Site
Cologne, North Rhine-Westphalia, 50937
About this study
Official title: A Phase II, Multicenter, Open-label Study of EGF816 in Combination With Nivolumab in Adult Patients With EGFR Mutated Non-small Cell Lung Cancer and of INC280 in Combination With Nivolumab in Adult Patients With cMet Positive Non-small Cell Lung Cancer
To determine the efficacy and safety of nivolumab in combination with EGF816 and of nivolumab in combination with INC280 in previously treated NSCLC patients
Read the detailed description
This was a phase II, multi-center, open-label study in patients with advanced non-small cell lung cancer (NSCLC). Patients were allocated based on their epidermal growth factor receptor (EGFR) status to one of the 2 groups: Group 1 - EGFR T790M NSCLC treated with EGF816 150 mg once daily (QD) + nivolumab 3 mg/kg every 2 weeks (Q2W), and Group 2 - EGFR wild type (wt) NSCLC treated with INC280 400 mg twice daily (BID) + nivolumab 3 mg/kg Q2W. Patients in Group 2 were subdivided into 2 subgroups based on c-Mesenchymal-epithelial transition (cMet) status: Subgroup A - high cMet (referred to as Group 2A) and Subgroup B- low cMet (referred to as Group 2B).
Patients could continue study treatment until patients experienced unacceptable toxicity that precluded any further treatment, disease progression and/or treatment was discontinued at the discretion of the investigator or withdrawal of consent, or the patient was transferred to a Novartis roll-over study or an alternative treatment option that could continue to provide study treatments. Following the approval of a protocol amendment, the maximum treatment duration for nivolumab could not exceed 2 years and patients who had received nivolumab beyond 2 years were discontinued from nivolumab treatment and continued on EGF816 or INC280 alone.
The primary objective of the trial was to estimate the clinical activity of nivolumab in combination with EGF816 or INC280.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- EGF816, INC280, Nivolumab
- Keywords
- Non small cell lung cancer, NSCLC, EGFR-mutated, EGF816, INC280, Nivolumab, EGFR-T790M NSCLC, EGFR wild-type (wt), cMET positive NSCLC, cMET negative NSCLC
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EGF816Drug
EGF816 150 mg once daily (QD) administered orally as a capsule
INC280Drug
INC280 400 mg twice daily (BID) administered orally as a tablet
NivolumabDrug
Nivolumab 3 mg/kg every 2 weeks (Q2W) administered by intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab and EGF816 | Experimental | Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W Receives: Drug: EGF816; Drug: Nivolumab |
| Nivolumab and INC280, high cMet | Experimental | Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W Receives: Drug: INC280; Drug: Nivolumab |
| Nivolumab and INC280, low cMet | Experimental | Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W Receives: Drug: INC280; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS) Rate at 6 Months Per RECIST v1.1
PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
PFS was modeled using a Weibull distribution and the PFS rate at 6 months was estimated from the posterior distribution.
Measured: 6 months
Secondary outcomes (18)
Overall Response Rate (ORR) Per RECIST v1.1
Tumor response was based on local investigator assessment as per RECIST v1.1. ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR).
For RECIST v1.1, 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; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: From start of treatment until end of treatment, assessed up to 4.7 years
Disease Control Rate (DCR) Per RECIST v1.1
Tumor response was based on local investigator assessment as per RECIST v1.1. DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD).
For RECIST v1.1, 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; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
Measured: From start of treatment until end of treatment, assessed up to 4.7 years
Median Progression-Free Survival (PFS) Per RECIST v1.1
PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. The median PFS was estimated using the Kaplan-Meier method.
Tumor response was based on local investigator assessment as per RECIST v1.1
Measured: From start of treatment to first documented progression or death, assessed up to 5 years
Progression-Free Survival (PFS) Rate at 3 Months Per RECIST v1.1
PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
The PFS rate at 3 months was estimated using the Kaplan-Meier method.
Measured: 3 months
Overall Survival (OS) at 1 Year
OS represents the percentage of participants who are alive after the start of study treatment. OS at 1 year was estimated using the Kaplan-Meier method.
Measured: 1 year
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.
AE grades were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Measured: From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years
Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab
Number of participants with at least one dose reduction of EGF816, INC280 or nivolumab and number of participants with at least one dose interruption of EGF816, INC280 or nivolumab.
Dose reduction was not allowed for nivolumab in this study.
Measured: From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years
Dose Intensity of EGF816 and INC280
Dose intensity (mg/day) of EGF816 and INC280 was calculated as actual cumulative dose in milligrams divided by duration of exposure in days.
Measured: From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years
Dose Intensity of Nivolumab
Dose intensity (mg/kg biweekly) of nivolumab was calculated as actual cumulative dose in mg/kg divided by duration of exposure in days and then multiplied by 14 days (2 weeks).
Measured: From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years
Maximum Observed Plasma Concentration (Cmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
Measured: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Time to Reach Maximum Plasma Concentration (Tmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose.
Measured: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Measured: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Minimum Observed Plasma Concentration (Cmin) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Cmin is defined as the minimum observed plasma concentration following a dose.
Measured: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Maximum Observed Plasma Concentration (Cmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
Measured: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Time to Reach Maximum Plasma Concentration (Tmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
Measured: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Measured: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Minimum Observed Plasma Concentration (Cmin) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Cmin is defined as the minimum observed plasma concentration following a dose.
Measured: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Pre-dose Serum Concentration of Nivolumab
Nivolumab serum concentrations were assessed in samples taken at pre-dose. Pre-dose samples were collected before the next dose administration.
Measured: pre-dose on Cycle 1 Day 1 (groups 2A and 2B only) and pre-dose on Cycle 1 Day 15 and Cycle 2 Day 1 (all groups). The duration of one cycle was 28 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2014 (estimated)
- Study start9 Feb 2015
- Primary completion23 Sep 2019
- Study completion5 Feb 2021
Why it stopped: Sponsor decision due to low patient recruitment caused by the change in the treatment landscape of NSCLC.
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies 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
- 64 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
- NCT02323126
- Sponsor's protocol ID
- CEGF816X2201C
- Other IDs
- 2014-003731-20, 2014
- Status last verified
- Jan 2022
- First submitted
- 18 Dec 2014
- Last updated
- 28 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- 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
Publications
Felip E, Metro G, Tan DSW, Wolf J, Mark M, Boyer M, Hughes BGM, Bearz A, Moro-Sibilot D, Le X, Puente J, Massuti B, Tiedt R, Wang Y, Xu C, Mardjuadi FI, Cobo M. Capmatinib plus nivolumab in pretreated patients with EGFR wild-type advanced non-small cell lung cancer. Lung Cancer. 2024 Jun;192:107820. doi: 10.1016/j.lungcan.2024.107820. Epub 2024 May 10.
PubMed 38763104
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multicenter, Open-label Study of EGF816 in Combination With Nivolumab in Adult Patients With EGFR Mutated Non-small Cell Lung Cancer and of INC280 in Combination With Nivolumab in Adult Patients With cMet Positive Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02323126
- Acronym / sponsor ID
- CEGF816X2201C
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- Non small cell lung cancer, NSCLC, EGFR-mutated, EGF816, INC280, Nivolumab, EGFR-T790M NSCLC, EGFR wild-type (wt)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision due to low patient recruitment caused by the change in the treatment landscape of NSCLC.
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 9 Feb 2015 (actual)
- Primary completion
- 23 Sep 2019 (actual)
- Study completion
- 5 Feb 2021 (actual)
- First posted
- 23 Dec 2014 (estimated)
- Results
- Posted 15 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the efficacy and safety of nivolumab in combination with EGF816 and of nivolumab in combination with INC280 in previously treated NSCLC patients
Detailed description
This was a phase II, multi-center, open-label study in patients with advanced non-small cell lung cancer (NSCLC). Patients were allocated based on their epidermal growth factor receptor (EGFR) status to one of the 2 groups: Group 1 - EGFR T790M NSCLC treated with EGF816 150 mg once daily (QD) + nivolumab 3 mg/kg every 2 weeks (Q2W), and Group 2 - EGFR wild type (wt) NSCLC treated with INC280 400 mg twice daily (BID) + nivolumab 3 mg/kg Q2W. Patients in Group 2 were subdivided into 2 subgroups based on c-Mesenchymal-epithelial transition (cMet) status: Subgroup A - high cMet (referred to as Group 2A) and Subgroup B- low cMet (referred to as Group 2B).
Patients could continue study treatment until patients experienced unacceptable toxicity that precluded any further treatment, disease progression and/or treatment was discontinued at the discretion of the investigator or withdrawal of consent, or the patient was transferred to a Novartis roll-over study or an alternative treatment option that could continue to provide study treatments. Following the approval of a protocol amendment, the maximum treatment duration for nivolumab could not exceed 2 years and patients who had received nivolumab beyond 2 years were discontinued from nivolumab treatment and continued on EGF816 or INC280 alone.
The primary objective of the trial was to estimate the clinical activity of nivolumab in combination with EGF816 or INC280.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Nivolumab and EGF816 | Experimental | Drug: EGF816, Drug: NivolumabGroup 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W |
| Nivolumab and INC280, high cMet | Experimental | Drug: INC280, Drug: NivolumabGroup 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W |
| Nivolumab and INC280, low cMet | Experimental | Drug: INC280, Drug: NivolumabGroup 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Written informed consent must be obtained prior to any screening procedures
- Presence of at least one measurable lesion according to RECIST v.1.1
- ECOG performance status ≤ 2
- Patients with histologically documented locally advanced, recurrent and/or metastatic NSCLC
- Tumor tissue for determination and/or confirmation of genetic pre-requisites (i.e. EGFR T790M positivity post progression on EGFR TKI for Group 1; cMet status for Group 2) must be provided for analysis
Key exclusion criteria (24 listed)
- Patients who have received more than one prior line of EGFR TKI therapy1 (applies only to Group 1)
- Previous treatment with a c-MET inhibitor or HGF-targeting therapy (applies only to Group 2)
- Patients with brain metastases. However, if radiation therapy and/or surgery has been completed and serial evaluation by CT (with contrast enhancement) or MRI over a minimum of one month demonstrates the disease to be stable and if the patient remains asymptomatic without the need for treatment with steroids
- Patients who require emergent use of systemic steroids, chronic use of prednisone (greater than 10mg or an equivalent steroid dose daily) or emergent surgery and/or radiotherapy.
- History of allergy or hypersensitivity to nivolumab components
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 |
|---|---|---|
| EGF816EGF816 150 mg once daily (QD) administered orally as a capsule | Drug | Nivolumab and EGF816 |
| INC280INC280 400 mg twice daily (BID) administered orally as a tablet | Drug | Nivolumab and INC280, high cMet, Nivolumab and INC280, low cMet |
| NivolumabNivolumab 3 mg/kg every 2 weeks (Q2W) administered by intravenous infusion | Drug | Nivolumab and EGF816, Nivolumab and INC280, high cMet, Nivolumab and INC280, low cMet |
Primary outcome
Progression-Free Survival (PFS) Rate at 6 Months Per RECIST v1.1
Time frame: 6 months
PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PFS was modeled using a Weibull distribution and the PFS rate at 6 months was estimated from the posterior distribution.
18 secondary outcomes
Overall Response Rate (ORR) Per RECIST v1.1
Time frame: From start of treatment until end of treatment, assessed up to 4.7 years
Disease Control Rate (DCR) Per RECIST v1.1
Time frame: From start of treatment until end of treatment, assessed up to 4.7 years
Median Progression-Free Survival (PFS) Per RECIST v1.1
Time frame: From start of treatment to first documented progression or death, assessed up to 5 years
Progression-Free Survival (PFS) Rate at 3 Months Per RECIST v1.1
Time frame: 3 months
Overall Survival (OS) at 1 Year
Time frame: 1 year
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years
Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab
Time frame: From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years
Dose Intensity of EGF816 and INC280
Time frame: From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years
Dose Intensity of Nivolumab
Time frame: From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years
Maximum Observed Plasma Concentration (Cmax) of EGF816
Time frame: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Time to Reach Maximum Plasma Concentration (Tmax) of EGF816
Time frame: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EGF816
Time frame: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Minimum Observed Plasma Concentration (Cmin) of EGF816
Time frame: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Maximum Observed Plasma Concentration (Cmax) of INC280
Time frame: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Time to Reach Maximum Plasma Concentration (Tmax) of INC280
Time frame: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of INC280
Time frame: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Minimum Observed Plasma Concentration (Cmin) of INC280
Time frame: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.
Pre-dose Serum Concentration of Nivolumab
Time frame: pre-dose on Cycle 1 Day 1 (groups 2A and 2B only) and pre-dose on Cycle 1 Day 15 and Cycle 2 Day 1 (all groups). The duration of one cycle was 28 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38763104Felip E, Metro G, Tan DSW, Wolf J, Mark M, Boyer M, Hughes BGM, Bearz A, Moro-Sibilot D, Le X, Puente J, Massuti B, Tiedt R, Wang Y, Xu C, Mardjuadi FI, Cobo M. Capmatinib plus nivolumab in pretreated patients with EGFR wild-type advanced non-small cell lung cancer. Lung Cancer. 2024 Jun;192:107820. doi: 10.1016/j.lungcan.2024.107820. Epub 2024 May 10.
- 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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Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
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
13 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EGF816, INC280 and Nivolumab in people with Non Small Cell Lung Cancer, run by Novartis Pharmaceuticals at 13 sites in 8 countries.
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 11 inclusion and 24 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: stopped early, as of the sponsor's last update on 28 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Spain, Australia, Italy, United States, France and 3 more countries. 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 15 Jun 2021). 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?
Progression-Free Survival (PFS) Rate at 6 Months Per RECIST v1.1 (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02323126, which also lists 1 linked publication.
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 28 Feb 2022.