Clincosm LogoSign in Get a demo

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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04323436
Collaborator
(none)
31
Enrollment
15
Locations
3
Arms
27.9
Anticipated Duration (Months)
2.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
31 participants
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 controlRun-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
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
Actual Study Start Date :
Aug 19, 2020
Anticipated Primary Completion Date :
Dec 16, 2022
Anticipated Study Completion Date :
Dec 16, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Run-in part

capmatinib in combination with spartalizumab

Drug: Spartalizumab
Concentrate for solution for infusion
Other Names:
  • PDR001

    • Drug: Capmatinib
    Film-coated tablet
    Other Names:
  • INC280

    		•
    Experimental: Randomized part - Arm 1 spartalizumab

    capmatinib in combination with spartalizumab

    Drug: Spartalizumab
    Concentrate for solution for infusion
    Other Names:
  • PDR001

    • Drug: Capmatinib
    Film-coated tablet
    Other Names:
  • INC280

    		•
    Experimental: Randomized part - Arm 2 placebo

    capmatinib in combination with placebo

    Drug: Capmatinib
    Film-coated tablet
    Other Names:
  • INC280

    • Drug: spartalizumab placebo
    dextrose 5% in water (D5W) for infusion
    Other Names:
  • PDR001 placebo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate by Investigator assessment as per RECIST 1.1 [2.5 years]

      Run-in part To evaluate the anti-tumor activity of capmatinib in combination with spartalizumab

    2. Progression Free survival (PFS) by BIRC as per RECIST 1.1 [6 years]

      Randomized part To compare the efficacy of capmatinib in combination with spartalizumab versus capmatinib plus placebo

    Secondary Outcome Measures

    1. Adverse events (AE) and Serious Adverse events (SAE) incidence [2.5 years]

      Run-in part To assess safety of capmatinib in combination with spartalizumab

    2. Number of patients with dose interruptions, reductions, and dose intensity [2.5 years]

      Run-in part To assess tolerability of capmatinib in combination with spartalizumab

    3. Efficacy measurements per RECIST 1.1 : Disease Control Rate (DCR) by investigator asessment [2.5 years]

      Run-in part Disease Control Rate (DCR) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab

    4. Efficacy measurements per RECIST 1.1 : Progression Free Survival (PFS) by investigator assessment [2.5 years]

      Run in part Progression Free Survival (PFS) to further evaluate the anti-tumor activity of capmatinib in combination with spartalizumab

    5. Pharmacokinetics (PK): Cmax [2.5 years]

      Run-in part To evaluate the PK of capmatinib and spartalizumab

    6. Pharmacokinetics (PK): Tmax [2.5 years]

      Run-in part To evaluate the PK of capmatinib and spartalizumab

    7. Pharmacokinetics (PK): AUClast [2.5 years]

      Run-in part To evaluate the PK of capmatinib and spartalizumab

    8. Pharmacokinetics (PK): AUCtau [2.5 years]

      Run-in part To evaluate the PK of capmatinib and spartalizumab

    9. Overall survival (OS) [12 years]

      Randomized part To compare overall survival of capmatinib in combination with spartalizumab versus capmatinib plus placebo

    10. Adverse events (AE) and Serious Adverse events (SAE) incidence [6 years]

      Randomized part To assess safety of capmatinib in combination with spartalizumab versus capmatinib plus placebo

    11. Number of patients with dose interruptions, reductions, and dose intensity [6 years]

      Randomized part To assess tolerability of capmatinib in combination with spartalizumab versus capmatinib plus placebo

    12. Efficacy measurements per RECIST 1.1: Progression Free Survival (PFS) by investigator assessment [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

    13. Efficacy measurements per RECIST 1.1: Disease Control Rate (DCR) by BIRC and investigator assessment [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

    14. Efficacy measurements per RECIST 1.1: Duration of Response (DOR) by BIRC and investigator assessment [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

    15. Efficacy measurements per RECIST 1.1: Overall Response Rate (ORR) by BIRC and investigator assessment [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

    16. Efficacy measurements per RECIST 1.1: Time to Response (TTR) by BIRC and investigator assessment [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

    17. Change from baseline in EORTC QLQ-C30 questionnaires [6 years]

      Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo

    18. Change from baseline in EQ-LC13 questionnaires [6 years]

      Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo

    19. Change from baseline in EQ-5D-5L questionnaires [6 years]

      Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo

    20. Time to definitive 10 points deterioration symptom scores for pain in chest, coughing and dyspnea per QLQ-LC13 questionnaire [6 years]

      Randomized part To evaluate patient reported outcomes of capmatinib in combination with spartalizumab versus capmatinib plus placebo

    21. Pharmacokinetics (PK): Cmax [6 years]

      Randomized part To evaluate the PK of capmatinib and spartalizumab

    22. Pharmacokinetics (PK): Tmax [6 years]

      Randomized part To evaluate the PK of capmatinib and spartalizumab

    23. Pharmacokinetics (PK): AUCtau [6 years]

      Randomized part To evaluate the PK of capmatinib and spartalizumab

    24. Pharmacokinetics (PK): AUClast. [6 years]

      Randomized part To evaluate the PK of capmatinib and spartalizumab

    25. Antidrug antibodies (ADA) prevalence at baseline on treatment with spartalizumab [6 years]

      Randomized part To evaluate the prevalence of immunogenicity of spartalizumab in combination with capmatinib

    26. Antidrug antibodies (ADA) incidence on treatment with spartalizumab [6 years]

      Randomized part To evaluate the incidence of immunogenicity of spartalizumab in combination with capmatinib

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Massachusetts General Hospital Liver and Kidney TX Boston Massachusetts United States 02114
    2 Novartis Investigative Site Leuven Belgium 3000
    3 Novartis Investigative Site Montreal Quebec Canada H4A 3J1
    4 Novartis Investigative Site Lille France 59000
    5 Novartis Investigative Site Paris France 75679
    6 Novartis Investigative Site Pierre Benite Cedex France 69495
    7 Novartis Investigative Site Berlin Germany 13125
    8 Novartis Investigative Site Gerlingen Germany 70839
    9 Novartis Investigative Site Koeln Germany 50937
    10 Novartis Investigative Site Tübingen Germany 72076
    11 Novartis Investigative Site Bologna BO Italy 40138
    12 Novartis Investigative Site Osaka Sayama Osaka Japan 589 8511
    13 Novartis Investigative Site Seoul Korea, Republic of 03080
    14 Novartis Investigative Site Barcelona Catalunya Spain 08036
    15 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46014

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT04323436
    Other Study ID Numbers:
    • CINC280J12201
    • 2019-003097-11
    First Posted:
    Mar 26, 2020
    Last Update Posted:
    Jun 14, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    capmatinib
    spartalizumab
    MET mutation
    EGFR wild-type
    ALK negative mutation
    Additional relevant MeSH terms:
    Carcinoma, Non-Small-Cell Lung
    Spartalizumab

    Study Results

    No Results Posted as of Jun 14, 2022