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NCT04139317

Safety and Efficacy of Capmatinib (INC280) Plus Pembrolizumab vs Pembrolizumab Alone in NSCLC With PD-L1≥ 50%

Terminated Phase 2 Results posted Last updated 9 October 2024
What this trial tests

Phase 2 trial testing Capmatinib in Non-small Cell Lung Cancer (NSCLC) in 76 participants. Terminated before completion.

Timeline
22 January 2020
Primary endpoint
14 January 2022
7 February 2023

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment76
Start date22 January 2020
Primary completion14 January 2022
Estimated completion7 February 2023
Sites36 locations across France, Hong Kong, Italy, Japan, Greece, Malaysia, India, Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Non-small Cell Lung Cancer (NSCLC). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-Free Survival (PFS) by Investigator Assessment as Per RECIST 1.1 Primary · Up to 1.3 years

PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. Tumor response was based on investigator assessment per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment, the start of a subsequent anti-neoplastic therapy (if any) or the date of sponsor's decision to discontinue capmatinib (applicable only to subjects on the combination arm). Due to the discontinuation of one of the investigational drugs (capmatin

GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W5.22.0 – NA
Pembrolizumab 200mg Q3W5.12.6 – NA
Overall Response Rate (ORR) by Investigator Assessment as Per RECIST 1.1 Secondary · Up to 1.3 years

Tumor response was based on local investigator assessment as RECIST v1.1. ORR per RECIST v1.1 is defined as the percentage of participants with a best overall response (BOR) of Complete Response (CR) or Partial Response (PR). For the capmatinib plus pembrolizumab arm, 21-Jan-2021 or any last adequate tumor assessment prior to that date was considered as the end of evaluation period for BOR. 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% d

GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W9.83.3 – 21.4
Pembrolizumab 200mg Q3W40.021.1 – 61.3
Disease Control Rate (DCR) by Investigator Assessment as Per RECIST 1.1 Secondary · Up to 1.3 years

Tumor response was based on local investigator assessment per RECIST v1.1. DCR is defined as the percentage of participants with a BOR of Complete Response (CR), Partial Response (PR), Stable Disease (SD), and non-CR/non-progressive disease (for subjects without target lesions). For the capmatinib plus pembrolizumab arm, 21-Jan-2021 or any last adequate tumor assessment prior to that date was considered as the end of evaluation period for BOR. 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 red

GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W37.324.1 – 51.9
Pembrolizumab 200mg Q3W60.038.7 – 78.9
Time to Response (TTR) by Investigator Assessment as Per RECIST 1.1 Secondary · Up to 1.3 years

TTR is defined as the time from the date of randomization to the first documented response of either complete response or partial response, which must be subsequently confirmed (although initial date of response is used, not date of confirmation). TTR was analyzed using the Kaplan-Meier method as defined in the statistical analysis plan.

GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3WNANA – NA
Pembrolizumab 200mg Q3WNANA – NA
Duration of Response (DOR) by Investigator Assessment as Per RECIST 1.1 Secondary · Up to 1.3 years

DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment of overall lesion response according to RECIST v1.1. DOR is defined as the time from the date of first documented response (confirmed CR or confirmed PR) to the date of first documented disease progression or death due to any cause. If a patient not had an event, duration was censored at the date of last adequate tumor assessment before the start of a new anticancer therapy, if any. DOR was analyzed using the Kaplan-Meier method as defined in th

GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3WNANA – NA
Pembrolizumab 200mg Q3WNANA – NA
Overall Survival (OS) Secondary · Up to 2.1 years

OS is defined as the time from the date of randomization to the date of death due to any cause. The requirement for survival follow-up period was removed following the discontinuation of one of the investigational drugs (capmatinib) in all subjects in the combination arm and the implementation of Protocol Amendment 03. OS was analyzed using the Kaplan-Meier method as defined in the statistical analysis plan.

GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3WNANA – NA
Pembrolizumab 200mg Q3WNANA – NA
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · From first dose of study treatment to 30 days after last dose, up to 2.1 years

Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.

AEs
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W49
Pembrolizumab 200mg Q3W25
Treatment-related AEs
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W45
Pembrolizumab 200mg Q3W18
SAEs
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W31
Pembrolizumab 200mg Q3W13
Treatment-related SAEs
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W18
Pembrolizumab 200mg Q3W1
AEs leading to discontinuation
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W18
Pembrolizumab 200mg Q3W5
Treatment-related AEs leading to discontinuation
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W17
Pembrolizumab 200mg Q3W2
AEs leading to dose reduction/interruption
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W34
Pembrolizumab 200mg Q3W7
Treatment-related AEs leading to dose reduction/interruption
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W24
Pembrolizumab 200mg Q3W2
Maximum Observed Plasma Concentration (Cmax) of Capmatinib Secondary · pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 2 Day 1. The duration of one cycle was 21 days.

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.

GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W2730± 155.9
Time to Reach Maximum Plasma Concentration (Tmax) of Capmatinib Secondary · pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 2 Day 1. The duration of one cycle was 21 days.

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.

GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W1.330 – 4.00
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Capmatinib Secondary · pre-dose and 1, 2, 4 and 8 hours after morning dose on Cycle 2 Day 1. The duration of one cycle was 21 days.

PK parameters were calculated based on capmatinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.

GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W4210± 232.8
Trough Serum Concentration (Ctrough) of Pembrolizumab Secondary · pre-dose on Cycle 2 Day 1, Cycle 3 Day 1, Cycle 6 Day 1 and Cycle 12 Day 1. The duration of one cycle was 21 days.

PK parameters were calculated based on pembrolizumab serum concentrations by using non-compartmental methods. Ctrough is defined as the concentration reached immediately before the next dose is administered. All drug concentrations below the lower limit of quantification were treated as zero for the calculation of PK parameters.

Cycle 2 Day 1
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W11.8± 37.5
Pembrolizumab 200mg Q3W10.6± 34.8
Cycle 3 Day 1
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W18.9± 51.9
Pembrolizumab 200mg Q3W18.2± 32.3
Cycle 6 Day 1
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W27.6± 66.5
Pembrolizumab 200mg Q3W36.8± 26.0
Cycle 12 Day 1
GroupValue95% CI
Pembrolizumab 200mg Q3W49.7± 10.0
Number of Participants With Anti-pembrolizumab Antibodies Secondary · Baseline (pre-dose), up to 8 months

Immunogenicity (IG) was evaluated in serum samples. The assay to quantify and assess the IG was a validated homogeneous enzyme-linked immunosorbent assay (ELISA). * ADA-negative at baseline: ADA-negative sample at baseline * ADA-positive at baseline: ADA-positive sample at baseline * ADA-negative post-baseline: patient with ADA-negative sample at baseline and at least 1 post baseline determinant sample, all of which are ADA-negative samples * ADA-positive post-baseline: patient with at least 1 ADA-positive sample post baseline

ADA-negative at baseline
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W37
Pembrolizumab 200mg Q3W18
ADA-positive at baseline
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W5
Pembrolizumab 200mg Q3W2
ADA-negative post-baseline
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W36
Pembrolizumab 200mg Q3W18
ADA-positive post-baseline
GroupValue95% CI
Capmatinib 400mg BID + Pembrolizumab 200mg Q3W6
Pembrolizumab 200mg Q3W2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from first dose of study treatment to 30 days after last dose, up to 2.1 years after start of treatment. Deaths were collected in the post-treatment survival follow-up from day 31 after last dose of study treatment until the requirement for survival follow-up was removed following the discontinuation of capmatinib in the combination arm (protocol amendment 03), up to 1.3 years after start of treatment. These are not considered AEs.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Capmatinib + Pembrolizumab - On-treatment
Serious: 26/51 (51%)
Deaths: 8/51
Pembrolizumab After Combination Treatment - On-treatment
Serious: 9/51 (18%)
Deaths: 2/51
Pembrolizumab - On-treatment
Serious: 13/25 (52%)
Deaths: 3/25
Capmatinib + Pembrolizumab - Post-treatment Survival Follow-up
Serious: 0
Deaths: 6/38
Pembrolizumab - Post-treatment Survival Follow-up
Serious: 0
Deaths: 5/20

Serious adverse events (51 terms)

ReactionSystemCapmatinib + Pembrolizumab…Pembrolizumab After Combin…Pembrolizumab - On-treatmentCapmatinib + Pembrolizumab…Pembrolizumab - Post-treat…
PyrexiaGeneral disorders
Pericardial effusionCardiac disorders
BronchitisInfections and infestations
PneumoniaInfections and infestations
SepsisInfections and infestations
Acute kidney injuryRenal and urinary disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Cardiac failureCardiac disorders
Cardiac failure congestiveCardiac disorders
Abdominal pain upperGastrointestinal disorders
IleusGastrointestinal disorders
PancreatitisGastrointestinal disorders
Pancreatitis acuteGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
Disease progressionGeneral disorders
General physical health deteriorationGeneral disorders
HepatotoxicityHepatobiliary disorders
HypertransaminasaemiaHepatobiliary disorders
Immune-mediated hepatitisHepatobiliary disorders
HypersensitivityImmune system disorders
CellulitisInfections and infestations
Other adverse events (58 terms — click to expand)

ReactionSystemCapmatinib + Pembrolizumab…Pembrolizumab After Combin…Pembrolizumab - On-treatmentCapmatinib + Pembrolizumab…Pembrolizumab - Post-treat…
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
NauseaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
PyrexiaGeneral disorders
DiarrhoeaGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
Blood creatinine increasedInvestigations
HypothyroidismEndocrine disorders
Blood bilirubin increasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HypertensionVascular disorders
AstheniaGeneral disorders
FatigueGeneral disorders
Blood alkaline phosphatase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
Amylase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
SARS-CoV-2 test negativeInvestigations
Back painMusculoskeletal and connective tissue disorders
ParaesthesiaNervous system disorders
InsomniaPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
Abdominal pain upperGastrointestinal disorders
Chest painGeneral disorders
ChillsGeneral disorders
Blood creatine phosphokinase increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
HypoaesthesiaNervous system disorders
Productive coughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Pyrexia, Pericardial effusion, Bronchitis, Pneumonia, Sepsis, Acute kidney injury, Chronic obstructive pulmonary disease, Dyspnoea.

Data from ClinicalTrials.gov NCT04139317 adverse events section.

Sponsor's own description

The purpose was to evaluate the efficacy and safety of the combination of capmatinib with pembrolizumab compared to pembrolizumab alone as first-line treatment for subjects with locally advanced or metastatic NSCLC who have PD-L1 expression ≥ 50% and have no EGFR mutation or ALK rearrangement. Capmatinib has demonstrated immunomodulatory activities when combined with an anti-PD1 antibody in preclinical tumor models irrespective of MET dysregulation. The combination of capmatinib with checkpoint inhibitors has been established to be tolerable and could provide additional clinical benefit to the subjects.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends.
    Majeed U, Manochakian R, Zhao Y, Lou Y. · · 2021 · cited 193× · PMID 34238332 · DOI 10.1186/s13045-021-01121-2
  2. Small molecule inhibitors targeting the cancers.
    Liu GH, Chen T, Zhang X, Ma XL, et al · · 2022 · cited 127× · PMID 36254250 · DOI 10.1002/mco2.181
  3. Neutrophils in the era of immune checkpoint blockade.
    Faget J, Peters S, Quantin X, Meylan E, et al · · 2021 · cited 94× · PMID 34301813 · DOI 10.1136/jitc-2020-002242
  4. Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.
    Cao Z, Quazi S, Arora S, Osellame LD, et al · · 2025 · cited 57× · PMID 39780187 · DOI 10.1186/s12929-024-01099-2
  5. Current and future treatment options for <i>MET</i> exon 14 skipping alterations in non-small cell lung cancer.
    Hong L, Zhang J, Heymach JV, Le X. · · 2021 · cited 50× · PMID 33643443 · DOI 10.1177/1758835921992976
  6. The METeoric rise of MET in lung cancer.
    Friedlaender A, Drilon A, Banna GL, Peters S, et al · · 2020 · cited 36× · PMID 32888330 · DOI 10.1002/cncr.33159
  7. MET Signaling Pathways, Resistance Mechanisms, and Opportunities for Target Therapies.
    Rivas S, Marín A, Samtani S, González-Feliú E, et al · · 2022 · cited 35× · PMID 36430388 · DOI 10.3390/ijms232213898
  8. Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion.
    Xia Y, Huang C, Zhong M, Zhong H, et al · · 2025 · cited 32× · PMID 39856684 · DOI 10.1186/s12964-025-02033-1

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