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Study of Capmatinib and Spartalizumab/Placebo in Advanced NSCLC Patients With MET Exon 14 Skipping Mutations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04323436
Recruitment Status : Active, not recruiting
First Posted : March 26, 2020
Last Update Posted : May 17, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE March 23, 2020
First Posted Date  ICMJE March 26, 2020
Last Update Posted Date May 17, 2022
Actual Study Start Date  ICMJE August 19, 2020
Estimated Primary Completion Date December 16, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 3, 2021)
  • Overall Response Rate by Investigator assessment as per RECIST 1.1 [ Time Frame: 2.5 years ]
    Run-in part To evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
  • Progression Free survival (PFS) by BIRC as per RECIST 1.1 [ Time Frame: 6 years ]
    Randomized part To compare the efficacy of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Original Primary Outcome Measures  ICMJE
 (submitted: March 24, 2020)
  • Overall Response Rate by Blinded Independent Review Committee (BIRC) as per RECIST 1.1 [ Time Frame: 4 years ]
    Run-in part To evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
  • Progression Free survival (PFS) by BIRC as per RECIST 1.1 [ Time Frame: 6 years ]
    Randomized part To compare the efficacy of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2021)
  • Adverse events (AE) and Serious Adverse events (SAE) incidence [ Time Frame: 2.5 years ]
    Run-in part To assess safety of capmatinib in combination with spartalizumab
  • Number of patients with dose interruptions, reductions, and dose intensity [ Time Frame: 2.5 years ]
    Run-in part To assess tolerability of capmatinib in combination with spartalizumab
  • Efficacy measurements per RECIST 1.1 : Disease Control Rate (DCR) by investigator asessment [ Time Frame: 2.5 years ]
    Run-in part Disease Control Rate (DCR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
  • Efficacy measurements per RECIST 1.1 : Progression Free Survival (PFS) by investigator assessment [ Time Frame: 2.5 years ]
    Run in part Progression Free Survival (PFS) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
  • Pharmacokinetics (PK): Cmax [ Time Frame: 2.5 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): Tmax [ Time Frame: 2.5 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): AUClast [ Time Frame: 2.5 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): AUCtau [ Time Frame: 2.5 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab
  • Overall survival (OS) [ Time Frame: 12 years ]
    Randomized part To compare overall survival of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Adverse events (AE) and Serious Adverse events (SAE) incidence [ Time Frame: 6 years ]
    Randomized part To assess safety of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Number of patients with dose interruptions, reductions, and dose intensity [ Time Frame: 6 years ]
    Randomized part To assess tolerability of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Efficacy measurements per RECIST 1.1: Progression Free Survival (PFS) by investigator assessment [ Time Frame: 6 years ]
    Randomized part Progression Free Survival (PFS) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Efficacy measurements per RECIST 1.1: Disease Control Rate (DCR) by BIRC and investigator assessment [ Time Frame: 6 years ]
    Randomized part Disease Control Rate (DCR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Efficacy measurements per RECIST 1.1: Duration of Response (DOR) by BIRC and investigator assessment [ Time Frame: 6 years ]
    Randomized part Duration of Response (DOR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Efficacy measurements per RECIST 1.1: Overall Response Rate (ORR) by BIRC and investigator assessment [ Time Frame: 6 years ]
    Randomized part Overall Response Rate (ORR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Efficacy measurements per RECIST 1.1: Time to Response (TTR) by BIRC and investigator assessment [ Time Frame: 6 years ]
    Randomized part Time to Response (TTR) To further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Change from baseline in EORTC QLQ-C30 questionnaires [ Time Frame: 6 years ]
    Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Change from baseline in EQ-LC13 questionnaires [ Time Frame: 6 years ]
    Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Change from baseline in EQ-5D-5L questionnaires [ Time Frame: 6 years ]
    Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire [ Time Frame: 6 years ]
    Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Pharmacokinetics (PK): Cmax [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): Tmax [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): AUCtau [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): AUClast. [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab
  • Antidrug antibodies (ADA) prevalence at baseline on treatment with spartalizumab [ Time Frame: 6 years ]
    Randomized part To evaluate the prevalence of immunogenicity of spartalizumab in combination with capmatinib
  • Antidrug antibodies (ADA) incidence on treatment with spartalizumab [ Time Frame: 6 years ]
    Randomized part To evaluate the incidence of immunogenicity of spartalizumab in combination with capmatinib
Original Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2020)
  • Adverse events (AE) and Serious Adverse events (SAE) incidence [ Time Frame: 4 years ]
    Run-in part To assess safety of capmatinib in combination with spartalizumab
  • Number of patients with dose interruptions, reductions, and dose intensity [ Time Frame: 4 years ]
    Run-in part To assess tolerability of capmatinib in combination with spartalizumab
  • Efficacy measurements per RECIST 1.1: Overall Response Rate (ORR) [ Time Frame: 4 years ]
    Run-in part Overall Response Rate (ORR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
  • Efficacy measurements per RECIST 1.1 : Disease Control Rate (DCR) by BIRC and investigator asessment [ Time Frame: 4 years ]
    Run-in part Disease Control Rate (DCR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
  • Efficacy measurements per RECIST 1.1 : Duration of Response (DOR) by BIRC and investigator assessment [ Time Frame: 4 years ]
    Run in part Duration of Response (DOR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
  • Efficacy measurements per RECIST 1.1 : Progression Free Survival (PFS) by BIRC and investigator assessment [ Time Frame: 4 years ]
    Run in part Progression Free Survival (PFS) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
  • Efficacy measurements per RECIST 1.1: Time to Response (TTR) by BIRC and investigator assessment [ Time Frame: 4 years ]
    Run in part Time to Response (TTR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
  • Overall Survival (OS) [ Time Frame: 4 years ]
    Run-in part To assess the overall survival
  • Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire [ Time Frame: 4 years ]
    Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab
  • Change from baseline in EORTC QLQ-C30 questionnaires [ Time Frame: 4 years ]
    Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab
  • Change from baseline in QLQ-LC13 questionnaires [ Time Frame: 4 years ]
    Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab
  • Change from baseline in EQ-5D-5L questionnaires [ Time Frame: 4 years ]
    Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab
  • Pharmacokinetics (PK): Cmax [ Time Frame: 4 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): Tmax [ Time Frame: 4 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): AUClast [ Time Frame: 4 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): AUCtau [ Time Frame: 4 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab
  • Antidrug antibody (ADA) prevalence on treatment with spartalizumab [ Time Frame: 4 years ]
    Run-in part To evaluate the prevalence of immunogenicity of spartalizumab in combination with capmatinib
  • Antidrug antibody (ADA) incidence on treatment with spartalizumab [ Time Frame: 4 years ]
    Run-in part To evaluate the incidence of immunogenicity of spartalizumab in combination with capmatinib
  • Overall survival (OS) [ Time Frame: 12 years ]
    Randomized part To compare overall survival of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Adverse events (AE) and Serious Adverse events (SAE) incidence [ Time Frame: 6 years ]
    Randomized part To assess safety of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Number of patients with dose interruptions, reductions, and dose intensity [ Time Frame: 6 years ]
    Randomized part To assess tolerability of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Efficacy measurements per RECIST 1.1: Progression Free Survival (PFS) by investigator assessment [ Time Frame: 6 years ]
    Randomized part Progression Free Survival (PFS) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Efficacy measurements per RECIST 1.1: Disease Control Rate (DCR) by BIRC and investigator assessment [ Time Frame: 6 years ]
    Randomized part Disease Control Rate (DCR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Efficacy measurements per RECIST 1.1: Duration of Response (DOR) by BIRC and investigator assessment [ Time Frame: 6 years ]
    Randomized part Duration of Response (DOR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Efficacy measurements per RECIST 1.1: Overall Response Rate (ORR) by BIRC and investigator assessment [ Time Frame: 6 years ]
    Randomized part Overall Response Rate (ORR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Efficacy measurements per RECIST 1.1: Time to Response (TTR) by BIRC and investigator assessment [ Time Frame: 6 years ]
    Randomized part Time to Response (TTR) To further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Change from baseline in EORTC QLQ-C30 questionnaires [ Time Frame: 6 years ]
    Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Change from baseline in EQ-LC13 questionnaires [ Time Frame: 6 years ]
    Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Change from baseline in EQ-5D-5L questionnaires [ Time Frame: 6 years ]
    Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire [ Time Frame: 6 years ]
    Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
  • Pharmacokinetics (PK): Cmax [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): Tmax [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): AUCtau [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab
  • Pharmacokinetics (PK): AUClast. [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab
  • Antidrug antibodies (ADA) prevalence at baseline on treatment with spartalizumab [ Time Frame: 6 years ]
    Randomized part To evaluate the prevalence of immunogenicity of spartalizumab in combination with capmatinib
  • Antidrug antibodies (ADA) incidence on treatment with spartalizumab [ Time Frame: 6 years ]
    Randomized part To evaluate the incidence of immunogenicity of spartalizumab in combination with capmatinib
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Capmatinib and Spartalizumab/Placebo in Advanced NSCLC Patients With MET Exon 14 Skipping Mutations
Official Title  ICMJE 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
Brief 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 skipping (METΔex14) mutations
Detailed Description

The purpose of this study is 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) will be 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) will 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 is 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 will not be initiated.

Immediately following the enrollment halt:

  • All ongoing subjects were discontinued from spartalizumab treatment and continue to receive single agent capmatinib, given the proven tolerability and efficacy of capmatinib monotherapy in this study indication.
  • Enrolled subjects who had not started study treatment were to receive capmatinib single agent treatment from the start
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Run-in part: single arm, open-label.

Randomized part: two-arms parallel assignment, double-blinded, placebo control

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: Spartalizumab
    Concentrate for solution for infusion
    Other Name: PDR001
  • Drug: Capmatinib
    Film-coated tablet
    Other Name: INC280
  • Drug: spartalizumab placebo
    dextrose 5% in water (D5W) for infusion
    Other Name: PDR001 placebo
Study Arms  ICMJE
  • Experimental: Run-in part
    capmatinib in combination with spartalizumab
    Interventions:
    • Drug: Spartalizumab
    • Drug: Capmatinib
  • Experimental: Randomized part - Arm 1 spartalizumab
    capmatinib in combination with spartalizumab
    Interventions:
    • Drug: Spartalizumab
    • Drug: Capmatinib
  • Experimental: Randomized part - Arm 2 placebo
    capmatinib in combination with placebo
    Interventions:
    • Drug: Capmatinib
    • Drug: spartalizumab placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 11, 2021)
31
Original Estimated Enrollment  ICMJE
 (submitted: March 24, 2020)
270
Estimated Study Completion Date  ICMJE December 16, 2022
Estimated Primary Completion Date December 16, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • 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:

  • 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)

Other inclusion and exclusion criteras may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04323436
Other Study ID Numbers  ICMJE CINC280J12201
2019-003097-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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.
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP