Clinical Trials /

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

NCT04323436

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CINC280J12201
  • NCT ID: NCT04323436

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
SpartalizumabPDR001Randomized part - Arm 1 spartalizumab
CapmatinibINC280Randomized part - Arm 1 spartalizumab
spartalizumab placeboPDR001 placeboRandomized part - Arm 2 placebo

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Run-in partExperimentalcapmatinib in combination with spartalizumab
  • Spartalizumab
  • Capmatinib
Randomized part - Arm 1 spartalizumabExperimentalcapmatinib in combination with spartalizumab
  • Spartalizumab
  • Capmatinib
Randomized part - Arm 2 placeboExperimentalcapmatinib in combination with placebo
  • Capmatinib
  • spartalizumab placebo

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate by Blinded Independent Review Committee (BIRC) as per RECIST 1.1
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate the anti-tumor activity of capmatinib in combination with spartalizumab

Secondary Outcome Measures

Measure:Adverse events (AE) and Serious Adverse events (SAE) incidence
Time Frame:4 years
Safety Issue:
Description:Run-in part To assess safety of capmatinib in combination with spartalizumab
Measure:Number of patients with dose interruptions, reductions, and dose intensity
Time Frame:4 years
Safety Issue:
Description:Run-in part To assess tolerability of capmatinib in combination with spartalizumab
Measure:Efficacy measurements per RECIST 1.1: Overall Response Rate (ORR)
Time Frame:4 years
Safety Issue:
Description:Run-in part Overall Response Rate (ORR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
Measure:Efficacy measurements per RECIST 1.1 : Disease Control Rate (DCR) by BIRC and investigator asessment
Time Frame:4 years
Safety Issue:
Description:Run-in part Disease Control Rate (DCR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
Measure:Efficacy measurements per RECIST 1.1 : Duration of Response (DOR) by BIRC and investigator assessment
Time Frame:4 years
Safety Issue:
Description:Run in part Duration of Response (DOR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
Measure:Efficacy measurements per RECIST 1.1 : Progression Free Survival (PFS) by BIRC and investigator assessment
Time Frame:4 years
Safety Issue:
Description:Run in part Progression Free Survival (PFS) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
Measure:Efficacy measurements per RECIST 1.1: Time to Response (TTR) by BIRC and investigator assessment
Time Frame:4 years
Safety Issue:
Description:Run in part Time to Response (TTR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab
Measure:Overall Survival (OS)
Time Frame:4 years
Safety Issue:
Description:Run-in part To assess the overall survival
Measure:Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab
Measure:Change from baseline in EORTC QLQ-C30 questionnaires
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab
Measure:Change from baseline in QLQ-LC13 questionnaires
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab
Measure:Change from baseline in EQ-5D-5L questionnaires
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab
Measure:Pharmacokinetics (PK): Cmax
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate the PK of capmatinib and spartalizumab
Measure:Pharmacokinetics (PK): Tmax
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate the PK of capmatinib and spartalizumab
Measure:Pharmacokinetics (PK): AUClast
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate the PK of capmatinib and spartalizumab
Measure:Pharmacokinetics (PK): AUCtau
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate the PK of capmatinib and spartalizumab
Measure:Antidrug antibody (ADA) prevalence on treatment with spartalizumab
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate the prevalence of immunogenicity of spartalizumab in combination with capmatinib
Measure:Antidrug antibody (ADA) incidence on treatment with spartalizumab
Time Frame:4 years
Safety Issue:
Description:Run-in part To evaluate the incidence of immunogenicity of spartalizumab in combination with capmatinib
Measure:Overall survival (OS)
Time Frame:12 years
Safety Issue:
Description:Randomized part To compare overall survival of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Adverse events (AE) and Serious Adverse events (SAE) incidence
Time Frame:6 years
Safety Issue:
Description:Randomized part To assess safety of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Number of patients with dose interruptions, reductions, and dose intensity
Time Frame:6 years
Safety Issue:
Description:Randomized part To assess tolerability of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Efficacy measurements per RECIST 1.1: Progression Free Survival (PFS) by investigator assessment
Time Frame:6 years
Safety Issue:
Description:Randomized part Progression Free Survival (PFS) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Efficacy measurements per RECIST 1.1: Disease Control Rate (DCR) by BIRC and investigator assessment
Time Frame:6 years
Safety Issue:
Description:Randomized part Disease Control Rate (DCR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Efficacy measurements per RECIST 1.1: Duration of Response (DOR) by BIRC and investigator assessment
Time Frame:6 years
Safety Issue:
Description:Randomized part Duration of Response (DOR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Efficacy measurements per RECIST 1.1: Overall Response Rate (ORR) by BIRC and investigator assessment
Time Frame:6 years
Safety Issue:
Description:Randomized part Overall Response Rate (ORR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Efficacy measurements per RECIST 1.1: Time to Response (TTR) by BIRC and investigator assessment
Time Frame:6 years
Safety Issue:
Description:Randomized part Time to Response (TTR) To further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Change from baseline in EORTC QLQ-C30 questionnaires
Time Frame:6 years
Safety Issue:
Description:Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Change from baseline in EQ-LC13 questionnaires
Time Frame:6 years
Safety Issue:
Description:Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Change from baseline in EQ-5D-5L questionnaires
Time Frame:6 years
Safety Issue:
Description:Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire
Time Frame:6 years
Safety Issue:
Description:Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo
Measure:Pharmacokinetics (PK): Cmax
Time Frame:6 years
Safety Issue:
Description:Randomized part To evaluate the PK of capmatinib and spartalizumab
Measure:Pharmacokinetics (PK): Tmax
Time Frame:6 years
Safety Issue:
Description:Randomized part To evaluate the PK of capmatinib and spartalizumab
Measure:Pharmacokinetics (PK): AUCtau
Time Frame:6 years
Safety Issue:
Description:Randomized part To evaluate the PK of capmatinib and spartalizumab
Measure:Pharmacokinetics (PK): AUClast.
Time Frame:6 years
Safety Issue:
Description:Randomized part To evaluate the PK of capmatinib and spartalizumab
Measure:Antidrug antibodies (ADA) prevalence at baseline on treatment with spartalizumab
Time Frame:6 years
Safety Issue:
Description:Randomized part To evaluate the prevalence of immunogenicity of spartalizumab in combination with capmatinib
Measure:Antidrug antibodies (ADA) incidence on treatment with spartalizumab
Time Frame:6 years
Safety Issue:
Description:Randomized part To evaluate the incidence of immunogenicity of spartalizumab in combination with capmatinib

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • capmatinib
  • spartalizumab
  • MET mutation
  • EGFR wild-type
  • ALK negative mutation

Last Updated

October 11, 2020