Carcinoma, Non-Small-Cell LungPhase 2NCT04323436
Study of Capmatinib and Spartalizumab/Placebo in Advanced NSCLC Patients With MET Exon 14 Skipping Mutations
A Phase 2 study testing Spartalizumab and Capmatinib in people with Carcinoma, Non-Small-Cell Lung, run by Novartis Pharmaceuticals at 15 sites in 9 countries.
Trial summary
A double-blind, placebo controlled, randomized, phase II study evaluating the efficacy and safety of capmatinib (INC280) and spartalizumab (PDR001) combination therapy versus capmatinib and placebo as first line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) patients with MET exon 14… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Spartalizumab and Capmatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 15 sitesin 9 countries
- Study dates
- 19 Aug 2020to 26 Jan 2023
- 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
- Histologically confirmed locally advanced or metastatic NSCLC which is EGFR wild-type, ALK rearrangement negative and METΔex14 mutated
- No prior systemic therapy for advanced/metastatic disease (neo-adjuvant/adjuvant treatment completed > 12 months before relapse are permitted)
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Measurable disease as per RECIST 1.1
- Known PD-L1 tumor expression status (applicable to Randomized part 2 only)
Who cannot join
- Prior treatment with a PD-1/PD-L1 inhibitor, MET inhibitor or HGF inhibitor
- Presence of symptomatic CNS metastases or requiring local CNS-directed therapy (radiotherapy or surgery), or increasing doses of corticosteroids 2 weeks prior to study entry
- Impaired cardiac function or clinically significant cardiac disease
- Presence or history of interstitial lung disease, non-infectious pneumonitis or interstitial pneumonitis, including clinically significant radiation pneumonitis
- History of allogenic bone marrow or solid organ transplant
- Radiotherapy to lung fields ≤ 4 weeks or to any other anatomic site ≤ 2 weeks prior to start of study treatment (palliative radiotherapy for bone lesions is allowed)
Trial locations and contacts
15 sites in 9 countries.
15 sites in 9 countries
Germany4 sites
Novartis Investigative Site
Berlin, 13125
Novartis Investigative Site
Cologne, 50937
Novartis Investigative Site
Gerlingen, 70839
Novartis Investigative Site
Tübingen, 72076
France3 sites
Novartis Investigative Site
Lille, 59000
Novartis Investigative Site
Paris, 75014
Novartis Investigative Site
Pierre-Bénite, 69495
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Valencia, Valencia, 46014
United States1 site
Massachusetts General Hospital Liver and Kidney TX
Boston, Massachusetts, 02114
About this study
Official title: A Double-blind, Placebo Controlled, Randomized, Phase II Study Evaluating the Efficacy and Safety of Capmatinib and Spartalizumab vs Capmatinib and Placebo as 1st Line Treatment for Advanced NSCLC Patients With MET exon14 Skipping Mutations
A double-blind, placebo controlled, randomized, phase II study evaluating the efficacy and safety of capmatinib (INC280) and spartalizumab (PDR001) combination therapy versus capmatinib and placebo as first line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping (METΔex14) mutations
Read the detailed description
The purpose of this study was to evaluate the efficacy and safety of capmatinib in combination with spartalizumab in treatment naive patients with EGFR wild-type, ALK rearrangement negative advanced NSCLC, harboring METΔex14 mutations.
A run-in part (Part 1) was conducted to determine the anti-tumor activity and safety of capmatinib in combination with spartalizumab. Upon review of safety data and confirmation of anti-tumor activity in Part 1, the randomized part (Part 2) was planned to be initiated to compare the efficacy and safety of capmatinib plus spartalizumab to capmatinib plus placebo.
Combined treatment of METΔex14 mutated NSCLC with capmatinib and spartalizumab was expected to result in improved efficacy compared to each single agent due to direct targeting of an oncogenic driver (MET) as well as more efficient stimulation of an anti-tumor immune response than with PD-1 blockade alone.
The study enrollment was halted on 28-Jul-2021 per sponsor's decision. The enrollment halt decision was based on lack of tolerability observed in capmatinib and spartalizumab combination treatment in the run-in part (Part 1) of the trial.
Following the study enrollment halt during Part 1 (Run in Part), Part 2 was not initiated.
Immediately following the enrollment halt:
- All ongoing subjects were discontinued from spartalizumab treatment and continue to receive single agent capmatinib
- Enrolled subjects who had not started study treatment were to receive capmatinib single agent treatment from the start
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Spartalizumab, Capmatinib, spartalizumab placebo
- Keywords
- capmatinib, spartalizumab, MET mutation, EGFR wild-type, ALK negative mutation
- 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.
SpartalizumabDrug
Also called PDR001
Concentrate for solution for infusion
CapmatinibDrug
Also called INC280
Film-coated tablet
spartalizumab placeboDrug
Also called PDR001 placebo
dextrose 5% in water (D5W) for infusion
| Study group | Role | What they receive |
|---|---|---|
| Run-in part | Experimental | capmatinib in combination with spartalizumab Receives: Drug: Spartalizumab; Drug: Capmatinib |
| Randomized part - Arm 1 spartalizumab | Experimental | capmatinib in combination with spartalizumab Receives: Drug: Spartalizumab; Drug: Capmatinib |
| Randomized part - Arm 2 placebo | Experimental | capmatinib in combination with placebo Receives: Drug: Capmatinib; Drug: spartalizumab placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Run-in Part: Overall Response Rate (ORR) by Investigator Assessment as Per RECIST 1.1
Tumor response was based on local investigator assessment as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. ORR per RECIST v1.1 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: Up to approximately 2 years and 4 months
Randomized Part: Progression-Free Survival (PFS) by BIRC as Per RECIST 1.1
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Tumor response based on blinded independent review committee (BIRC) assessment per RECIST v1.1.
Measured: Up to 6 years
Secondary outcomes (32)
Run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib
Number of participants with at least one dose reduction of capmatinib and number of participants with at least one dose interruption of capmatinib.
Measured: From first dose of capmatinib to last dose, up to 2.4 years
Run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of Spartalizumab
Number of participants with at least one dose reduction of spartalizumab and number of participants with at least one dose interruption of spartalizumab. Dose reductions were not allowed for spartalizumab.
Measured: From first dose of spartalizumab to last dose, up to 0.9 years
Run-in Part: Dose Intensity of Capmatinib
Dose intensity of capmatinib was calculated as actual cumulative dose in milligrams divided by duration of exposure in days.
Measured: From first dose of capmatinib to last dose, up to 2.4 years
Run-in Part: Dose Intensity of Spartalizumab
Dose intensity of spartalizumab was calculated as actual cumulative dose in milligrams divided by duration of exposure in days and then multiplied by the duration of one cycle (28 days).
Measured: From first dose of spartalizumab to last dose, up to 0.9 years
Run-in Part: Disease Control Rate (DCR) by Investigator Assessment as Per RECIST 1.1
DCR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), and non-CR/non-progressive disease (for subjects without target lesions). Tumor response was based on local investigator assessment per RECIST v1.1.
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; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression).
Measured: Up to approximately 2 years and 4 months
Run-in Part: Progression-Free Survival (PFS) by Investigator Assessment as Per RECIST 1.1
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on investigator assessment per RECIST v1.1. Progression is defined using RECIST v1.1 as at least 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.
PFS was analyzed using Kaplan-Meier estimates.
Measured: Up to approximately 2 years and 5 months
Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Capmatinib
Pharmacokinetic (PK) parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
Measured: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
Run-in Part: Time to Reach Maximum Plasma Concentration (Tmax) of Capmatinib
PK parameters were calculated based on capmatinib 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 and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
Run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the End of a Dosing Interval (AUCtau) of Capmatinib
PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUCtau calculation. A dosing interval (tau) is defined as 12 hours. The portion of area under the curve between 8 hours and 12 hours post-dose was calculated by extrapolation based on terminal elimination slop.
Measured: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
Run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Capmatinib
PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Measured: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
Run-in Part: Maximum Observed Serum Concentration (Cmax) of Spartalizumab
Pharmacokinetic (PK) parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Measured: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
Run-in Part: Time to Reach Maximum Serum Concentration (Tmax) of Spartalizumab
PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Measured: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
Run-in Part: Area Under the Serum Concentration-time Curve From Time Zero to the End of a Dosing Interval (AUCtau) of Spartalizumab
PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUCtau calculation. A dosing interval (tau) is defined as 28 days.
Measured: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
Run-in Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Spartalizumab
PK parameters were calculated based on spartalizumab serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.
Measured: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
Randomized Part: Overall Survival (OS)
OS is defined as the time from date of start of treatment to date of death due to any cause.
Measured: Up to 12 years
Randomized Part: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib and Spartalizumab
Number of participants with at least one dose reduction of capmatinib and spartalizumab and number of participants with at least one dose interruption of capmatinib and spartalizumab.
Measured: Up to 6 years
Randomized Part: Dose Intensity of Capmatinib and Spartalizumab
Dose intensity is defined as the ratio of actual cumulative dose and duration of exposure.
Measured: Up to 6 years
Randomized Part: Progression-Free Survival (PFS) by Investigator Assessment as Per RECIST 1.1
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Tumor response based on investigator assessment per RECIST v1.1.
Measured: Up to 6 years
Randomized Part: Disease Control Rate (DCR) by BIRC and Investigator Assessment as Per RECIST 1.1
DCR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), and non-CR/non-progressive disease (for subjects without target lesions). Tumor response based on BIRC and local investigator assessment per RECIST v1.1.
Measured: Up to 6 years
Randomized Part: Overall Response Rate (ORR) by BIRC and Investigator Assessment as Per RECIST 1.1
ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) and Partial Response (PR). Tumor response based on BIRC and local investigator assessment per RECIST v1.1.
Measured: Up to 6 years
Randomized Part: Duration of Response (DOR) by BIRC and Investigator Assessment as Per RECIST 1.1
DOR is defined as the time from the date of first documented response (CR or PR) to the first documented progression per RECIST 1.1 or death due to any cause.
Measured: Up to 6 years
Randomized Part: Time to Response (TTR) by BIRC and Investigator Assessment as Per RECIST 1.1
TTR is defined as the time from the date of start of treatment to the first documented response of either CR or PR, which must be subsequently confirmed, according to RECIST 1.1.
Measured: Up to 6 years
Randomized Part: Change From Baseline in EORTC QLQ-C30
The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items and is composed of both multi-item scales and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/QoL scale. All scales and single-item measures range in score from 0 to 100. For the functional and the global QoL scales, a higher score indicates better health. For the symptom scales, a higher score indicates more symptom burden. The QLQ-C30 summary score (0-100) is calculated as the mean of 13 of the 15 QLQ-C30 scale and item scores (excluding global QoL and financial impact), with a higher score indicating a better health-related QoL.
Measured: Up to 6 years
Randomized Part: Change From Baseline in EORTC QLQ-LC13
EORTC QLQ-LC13 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The five domains of the LC13 include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from "not at all" to "very much". Pain score is based on its presence, hence yes or no. Scores are averaged and transformed to 0 to 100. A higher score indicates a higher presence of symptoms.
Measured: Up to 6 years
Randomized Part: Change From Baseline in EQ-5D-5L
The EQ-5D-5L is a standardized measure of health utility that provides a single index value for one's health status. The EQ-5D-5L contains one item for each of five dimensions of health-related quality of life (HRQOL) (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Response options for each item vary from having no problems to extreme problems. Subject responses to the five dimensions of HRQOL reflect a specific health state that corresponds to a population preference weight for that state on a continuous scale of 0 (death) to 1 (perfect health). A visual analog scale (ranging from 0 to 100) is also included to capture subject's rating of their overall health status. Higher scores of the EQ-5D-5L represent better health states.
Measured: Up to 6 years
Randomized Part: Time to Definitive 10 Points Deterioration Symptom Scores for Pain in Chest, Coughing and Dyspnea Per QLQ-LC13 Questionnaire
EORTC QLQ-LC13 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The five domains of the LC13 include pain in chest, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from "not at all" to "very much". Pain score is based on its presence, hence yes or no. Scores are averaged and transformed to 0 to 100. A higher score indicates a higher presence of symptoms.
The time to definitive 10 points deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the corresponding scale score or death due to any cause.
Measured: Up to 6 years
Randomized Part: Time to Definitive Deterioration in Global Health Status/QoL, Shortness of Breath and Pain Per EORTC QLQ-C30
The EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact) and a global health status/QoL scale. All scales and single-item measures range in score from 0 to 100. For the functional and the global QoL scales, a higher score indicates better health. For the symptom scales, a higher score indicates more symptom burden.
The time to definitive 10 points deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the corresponding scale score or death due to any cause.
Measured: Up to 6 years
Randomized Part: Maximum Observed Concentration (Cmax) of Capmatinib and Spartalizumab
Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods. Cmax is defined as the maximum (peak) observed concentration following a dose.
Measured: Up to 6 years
Randomized Part: Time to Reach Maximum Concentration (Tmax) of Capmatinib and Spartalizumab
Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) concentration following a dose.
Measured: Up to 6 years
Randomized Part: Area Under the Concentration-time Curve From Time Zero to the End of a Dosing Interval (AUCtau) of Capmatinib and Spartalizumab
Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods.
Measured: Up to 6 years
Randomized Part: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Capmatinib and Spartalizumab
Pharmacokinetic (PK) parameters calculated based on capmatinib and spartalizumab concentrations in plasma and serum, respectively, by using non-compartmental methods.
Measured: Up to 6 years
Randomized Part: Number of Participants With Anti-spartalizumab Antibodies
Immunogenicity (IG) evaluated in serum samples. The assay to quantify and assess the IG was a validated homogeneous enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline (pre-dose), up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2020
- Study start19 Aug 2020
- Primary completion14 Dec 2022
- Study completion26 Jan 2023
Why it stopped: Study termination based on sponsor decision due to lack of tolerability observed with capmatinib and spartalizumab combination treatment when compared to data from capmatinib single agent studies
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 Carcinoma, Non-Small-Cell LungStudies 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Run-in part: single arm, open-label. Randomized part: two-arms parallel assignment, double-blinded, placebo control
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04323436
- Sponsor's protocol ID
- CINC280J12201
- Other IDs
- 2019-003097-11, 2019
- Status last verified
- Oct 2024
- First submitted
- 23 Mar 2020
- Last updated
- 9 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Placebo Controlled, Randomized, Phase II Study Evaluating the Efficacy and Safety of Capmatinib and Spartalizumab vs Capmatinib and Placebo as 1st Line Treatment for Advanced NSCLC Patients With MET exon14 Skipping Mutations
- ClinicalTrials.gov ID
- NCT04323436
- Acronym / sponsor ID
- CINC280J12201
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- capmatinib, spartalizumab, MET mutation, EGFR wild-type, ALK negative mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study termination based on sponsor decision due to lack of tolerability observed with capmatinib and spartalizumab combination treatment when compared to data from capmatinib single agent studies
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 19 Aug 2020 (actual)
- Primary completion
- 14 Dec 2022 (actual)
- Study completion
- 26 Jan 2023 (actual)
- First posted
- 26 Mar 2020 (actual)
- Results
- Posted 6 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A double-blind, placebo controlled, randomized, phase II study evaluating the efficacy and safety of capmatinib (INC280) and spartalizumab (PDR001) combination therapy versus capmatinib and placebo as first line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping (METΔex14) mutations
Detailed description
The purpose of this study was to evaluate the efficacy and safety of capmatinib in combination with spartalizumab in treatment naive patients with EGFR wild-type, ALK rearrangement negative advanced NSCLC, harboring METΔex14 mutations.
A run-in part (Part 1) was conducted to determine the anti-tumor activity and safety of capmatinib in combination with spartalizumab. Upon review of safety data and confirmation of anti-tumor activity in Part 1, the randomized part (Part 2) was planned to be initiated to compare the efficacy and safety of capmatinib plus spartalizumab to capmatinib plus placebo.
Combined treatment of METΔex14 mutated NSCLC with capmatinib and spartalizumab was expected to result in improved efficacy compared to each single agent due to direct targeting of an oncogenic driver (MET) as well as more efficient stimulation of an anti-tumor immune response than with PD-1 blockade alone.
The study enrollment was halted on 28-Jul-2021 per sponsor's decision. The enrollment halt decision was based on lack of tolerability observed in capmatinib and spartalizumab combination treatment in the run-in part (Part 1) of the trial.
Following the study enrollment halt during Part 1 (Run in Part), Part 2 was not initiated.
Immediately following the enrollment halt:
- All ongoing subjects were discontinued from spartalizumab treatment and continue to receive single agent capmatinib
- Enrolled subjects who had not started study treatment were to receive capmatinib single agent treatment from the start
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Run-in part: single arm, open-label. Randomized part: two-arms parallel assignment, double-blinded, placebo control
| Arm | Type | Receives |
|---|---|---|
| Run-in part | Experimental | Drug: Spartalizumab, Drug: Capmatinibcapmatinib in combination with spartalizumab |
| Randomized part - Arm 1 spartalizumab | Experimental | Drug: Spartalizumab, Drug: Capmatinibcapmatinib in combination with spartalizumab |
| Randomized part - Arm 2 placebo | Experimental | Drug: Capmatinib, Drug: spartalizumab placebocapmatinib in combination with placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically confirmed locally advanced or metastatic NSCLC which is EGFR wild-type, ALK rearrangement negative and METΔex14 mutated
- No prior systemic therapy for advanced/metastatic disease (neo-adjuvant/adjuvant treatment completed > 12 months before relapse are permitted)
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Measurable disease as per RECIST 1.1
- Known PD-L1 tumor expression status (applicable to Randomized part 2 only)
Key exclusion criteria (6 listed)
- Prior treatment with a PD-1/PD-L1 inhibitor, MET inhibitor or HGF inhibitor
- Presence of symptomatic CNS metastases or requiring local CNS-directed therapy (radiotherapy or surgery), or increasing doses of corticosteroids 2 weeks prior to study entry
- Impaired cardiac function or clinically significant cardiac disease
- Presence or history of interstitial lung disease, non-infectious pneumonitis or interstitial pneumonitis, including clinically significant radiation pneumonitis
- History of allogenic bone marrow or solid organ transplant
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 |
|---|---|---|
| SpartalizumabAlso: PDR001Concentrate for solution for infusion | Drug | Randomized part - Arm 1 spartalizumab, Run-in part |
| CapmatinibAlso: INC280Film-coated tablet | Drug | Randomized part - Arm 1 spartalizumab, Randomized part - Arm 2 placebo, Run-in part |
| spartalizumab placeboAlso: PDR001 placebodextrose 5% in water (D5W) for infusion | Drug | Randomized part - Arm 2 placebo |
Primary outcome
Run-in Part: Overall Response Rate (ORR) by Investigator Assessment as Per RECIST 1.1
Time frame: Up to approximately 2 years and 4 months
Tumor response was based on local investigator assessment as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. ORR per RECIST v1.1 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.
Randomized Part: Progression-Free Survival (PFS) by BIRC as Per RECIST 1.1
Time frame: Up to 6 years
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Tumor response based on blinded independent review committee (BIRC) assessment per RECIST v1.1.
32 secondary outcomes
Run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib
Time frame: From first dose of capmatinib to last dose, up to 2.4 years
Run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of Spartalizumab
Time frame: From first dose of spartalizumab to last dose, up to 0.9 years
Run-in Part: Dose Intensity of Capmatinib
Time frame: From first dose of capmatinib to last dose, up to 2.4 years
Run-in Part: Dose Intensity of Spartalizumab
Time frame: From first dose of spartalizumab to last dose, up to 0.9 years
Run-in Part: Disease Control Rate (DCR) by Investigator Assessment as Per RECIST 1.1
Time frame: Up to approximately 2 years and 4 months
Run-in Part: Progression-Free Survival (PFS) by Investigator Assessment as Per RECIST 1.1
Time frame: Up to approximately 2 years and 5 months
Run-in Part: Maximum Observed Plasma Concentration (Cmax) of Capmatinib
Time frame: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
Run-in Part: Time to Reach Maximum Plasma Concentration (Tmax) of Capmatinib
Time frame: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
Run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the End of a Dosing Interval (AUCtau) of Capmatinib
Time frame: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
Run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Capmatinib
Time frame: pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 3 Day 1. The duration of one cycle was 28 days.
Run-in Part: Maximum Observed Serum Concentration (Cmax) of Spartalizumab
Time frame: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
Run-in Part: Time to Reach Maximum Serum Concentration (Tmax) of Spartalizumab
Time frame: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
Run-in Part: Area Under the Serum Concentration-time Curve From Time Zero to the End of a Dosing Interval (AUCtau) of Spartalizumab
Time frame: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
Run-in Part: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Spartalizumab
Time frame: pre-infusion and 1, 72, 168, 336 and 672 hours after completion of the spartalizumab infusion on Cycle 3 Day 1. The duration of the infusion was approximately 30 minutes. The duration of one cycle was 28 days.
Randomized Part: Overall Survival (OS)
Time frame: Up to 12 years
Randomized Part: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib and Spartalizumab
Time frame: Up to 6 years
Randomized Part: Dose Intensity of Capmatinib and Spartalizumab
Time frame: Up to 6 years
Randomized Part: Progression-Free Survival (PFS) by Investigator Assessment as Per RECIST 1.1
Time frame: Up to 6 years
Randomized Part: Disease Control Rate (DCR) by BIRC and Investigator Assessment as Per RECIST 1.1
Time frame: Up to 6 years
Randomized Part: Overall Response Rate (ORR) by BIRC and Investigator Assessment as Per RECIST 1.1
Time frame: Up to 6 years
Randomized Part: Duration of Response (DOR) by BIRC and Investigator Assessment as Per RECIST 1.1
Time frame: Up to 6 years
Randomized Part: Time to Response (TTR) by BIRC and Investigator Assessment as Per RECIST 1.1
Time frame: Up to 6 years
Randomized Part: Change From Baseline in EORTC QLQ-C30
Time frame: Up to 6 years
Randomized Part: Change From Baseline in EORTC QLQ-LC13
Time frame: Up to 6 years
Randomized Part: Change From Baseline in EQ-5D-5L
Time frame: Up to 6 years
Randomized Part: Time to Definitive 10 Points Deterioration Symptom Scores for Pain in Chest, Coughing and Dyspnea Per QLQ-LC13 Questionnaire
Time frame: Up to 6 years
Randomized Part: Time to Definitive Deterioration in Global Health Status/QoL, Shortness of Breath and Pain Per EORTC QLQ-C30
Time frame: Up to 6 years
Randomized Part: Maximum Observed Concentration (Cmax) of Capmatinib and Spartalizumab
Time frame: Up to 6 years
Randomized Part: Time to Reach Maximum Concentration (Tmax) of Capmatinib and Spartalizumab
Time frame: Up to 6 years
Randomized Part: Area Under the Concentration-time Curve From Time Zero to the End of a Dosing Interval (AUCtau) of Capmatinib and Spartalizumab
Time frame: Up to 6 years
Randomized Part: Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Capmatinib and Spartalizumab
Time frame: Up to 6 years
Randomized Part: Number of Participants With Anti-spartalizumab Antibodies
Time frame: Baseline (pre-dose), up to 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- 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.
Related trials for Carcinoma, Non-Small-Cell Lung
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
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.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Spartalizumab and Capmatinib in people with Carcinoma, Non-Small-Cell Lung, run by Novartis Pharmaceuticals at 15 sites in 9 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 5 inclusion and 6 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 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Germany, France, Spain, United States, Belgium and 4 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 6 Feb 2024). 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?
Run-in Part: Overall Response Rate (ORR) by Investigator Assessment as Per RECIST 1.1 (time frame: Up to approximately 2 years and 4 months). The study lists 2 primary outcomes in all. 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 9 Oct 2024.