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 : 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

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

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

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

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

Original Estimated Enrollment ^ICMJE

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

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

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