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

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ClinicalTrials.gov Identifier: NCT04323436
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : May 7, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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
Carcinoma, Non-Small-Cell Lung Drug: Spartalizumab Drug: Capmatinib Drug: spartalizumab placebo 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 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 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 : August 19, 2020
Estimated Primary Completion Date : May 14, 2026
Estimated Study Completion Date : January 28, 2032

Resource links provided by the National Library of Medicine

Drug Information available for: Capmatinib

Arm Intervention/treatment
Experimental: Run-in part
capmatinib in combination with spartalizumab
Drug: Spartalizumab
Concentrate for solution for infusion
Other Name: PDR001

Drug: Capmatinib
Film-coated tablet
Other Name: INC280

Experimental: Randomized part - Arm 1 spartalizumab
capmatinib in combination with spartalizumab
Drug: Spartalizumab
Concentrate for solution for infusion
Other Name: PDR001

Drug: Capmatinib
Film-coated tablet
Other Name: INC280

Experimental: Randomized part - Arm 2 placebo
capmatinib in combination with placebo
Drug: Capmatinib
Film-coated tablet
Other Name: INC280

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




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Overall Survival (OS) [ Time Frame: 4 years ]
    Run-in part To assess the overall survival

  9. 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

  10. 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

  11. 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

  12. 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

  13. Pharmacokinetics (PK): Cmax [ Time Frame: 4 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab

  14. Pharmacokinetics (PK): Tmax [ Time Frame: 4 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab

  15. Pharmacokinetics (PK): AUClast [ Time Frame: 4 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab

  16. Pharmacokinetics (PK): AUCtau [ Time Frame: 4 years ]
    Run-in part To evaluate the PK of capmatinib and spartalizumab

  17. 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

  18. 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

  19. Overall survival (OS) [ Time Frame: 12 years ]
    Randomized part To compare overall survival of capmatinib in combination with spartalizumab versus capmatinib plus placebo

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. Pharmacokinetics (PK): Cmax [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab

  32. Pharmacokinetics (PK): Tmax [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab

  33. Pharmacokinetics (PK): AUCtau [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab

  34. Pharmacokinetics (PK): AUClast. [ Time Frame: 6 years ]
    Randomized part To evaluate the PK of capmatinib and spartalizumab

  35. 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

  36. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04323436


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Massachusetts
Massachusetts General Hospital Liver and Kidney TX Recruiting
Boston, Massachusetts, United States, 02114
Contact: Susan Symes    617-726-2631    ssymes@mgh.harvard.edu   
Principal Investigator: Rebecca Heist         
Belgium
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
Canada, Quebec
Novartis Investigative Site Recruiting
Montreal, Quebec, Canada, H4A 3J1
France
Novartis Investigative Site Recruiting
LILLE Cédex, France, 59037
Novartis Investigative Site Recruiting
Paris, France, 75679
Novartis Investigative Site Recruiting
Pierre Benite, France, 69495
Germany
Novartis Investigative Site Recruiting
Berlin, Germany, 13125
Novartis Investigative Site Recruiting
Gerlingen, Germany, 70839
Novartis Investigative Site Recruiting
Koeln, Germany, 50937
Novartis Investigative Site Recruiting
Tübingen, Germany, 72076
Italy
Novartis Investigative Site Recruiting
Verona, VR, Italy, 37126
Japan
Novartis Investigative Site Recruiting
Nagoya, Aichi, Japan, 464 8681
Novartis Investigative Site Recruiting
Osaka Sayama, Osaka, Japan, 589 8511
Novartis Investigative Site Recruiting
Sunto Gun, Shizuoka, Japan, 411 8777
Novartis Investigative Site Recruiting
Koto ku, Tokyo, Japan, 135 8550
Korea, Republic of
Novartis Investigative Site Recruiting
Gyeonggi do, Korea, Korea, Republic of, 10408
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03080
Spain
Novartis Investigative Site Recruiting
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
Valencia, Comunidad Valenciana, Spain, 46014
Novartis Investigative Site Recruiting
Madrid, Spain, 28034
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04323436    
Other Study ID Numbers: CINC280J12201
First Posted: March 26, 2020    Key Record Dates
Last Update Posted: May 7, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
capmatinib
spartalizumab
MET mutation
EGFR wild-type
ALK negative mutation
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases