NCT04323436

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

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Aug 2020

Geographic Reach
9 countries

15 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 23, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 26, 2020

Completed
5 months until next milestone

Study Start

First participant enrolled

August 19, 2020

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 14, 2022

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 26, 2023

Completed
1 year until next milestone

Results Posted

Study results publicly available

February 6, 2024

Completed
Last Updated

October 9, 2024

Status Verified

October 1, 2024

Enrollment Period

2.3 years

First QC Date

March 23, 2020

Results QC Date

November 30, 2023

Last Update Submit

October 7, 2024

Conditions

Keywords

capmatinibspartalizumabMET mutationEGFR wild-typeALK negative mutation

Outcome Measures

Primary Outcomes (2)

  • Run-in Part: Overall Response Rate (ORR) by Investigator Assessment as Per RECIST 1.1

    Tumor response was based on local investigator assessment as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. ORR per RECIST v1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Up to approximately 2 years and 4 months

  • Randomized Part: Progression-Free Survival (PFS) by BIRC as Per RECIST 1.1

    PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Tumor response based on blinded independent review committee (BIRC) assessment per RECIST v1.1.

    Up to 6 years

Secondary Outcomes (32)

  • Run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of Capmatinib

    From first dose of capmatinib to last dose, up to 2.4 years

  • Run-in Part: Number of Participants With Dose Reductions and Dose Interruptions of Spartalizumab

    From first dose of spartalizumab to last dose, up to 0.9 years

  • Run-in Part: Dose Intensity of Capmatinib

    From first dose of capmatinib to last dose, up to 2.4 years

  • Run-in Part: Dose Intensity of Spartalizumab

    From first dose of spartalizumab to last dose, up to 0.9 years

  • Run-in Part: Disease Control Rate (DCR) by Investigator Assessment as Per RECIST 1.1

    Up to approximately 2 years and 4 months

  • +27 more secondary outcomes

Study Arms (3)

Run-in part

EXPERIMENTAL

capmatinib in combination with spartalizumab

Drug: SpartalizumabDrug: Capmatinib

Randomized part - Arm 1 spartalizumab

EXPERIMENTAL

capmatinib in combination with spartalizumab

Drug: SpartalizumabDrug: Capmatinib

Randomized part - Arm 2 placebo

EXPERIMENTAL

capmatinib in combination with placebo

Drug: CapmatinibDrug: spartalizumab placebo

Interventions

Concentrate for solution for infusion

Also known as: PDR001
Randomized part - Arm 1 spartalizumabRun-in part

Film-coated tablet

Also known as: INC280
Randomized part - Arm 1 spartalizumabRandomized part - Arm 2 placeboRun-in part

dextrose 5% in water (D5W) for infusion

Also known as: PDR001 placebo
Randomized part - Arm 2 placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Massachusetts General Hospital Liver and Kidney TX

Boston, Massachusetts, 02114, United States

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Montreal, Quebec, H4A 3J1, Canada

Location

Novartis Investigative Site

Lille, 59000, France

Location

Novartis Investigative Site

Paris, 75014, France

Location

Novartis Investigative Site

Pierre-Bénite, 69495, France

Location

Novartis Investigative Site

Berlin, 13125, Germany

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Gerlingen, 70839, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Ōsaka-sayama, Osaka, 589 8511, Japan

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46014, Spain

Location

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

spartalizumabcapmatinib

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Results Point of Contact

Title
Study Director
Organization
Novartis

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Run-in part: single arm, open-label. Randomized part: two-arms parallel assignment, double-blinded, placebo control
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 23, 2020

First Posted

March 26, 2020

Study Start

August 19, 2020

Primary Completion

December 14, 2022

Study Completion

January 26, 2023

Last Updated

October 9, 2024

Results First Posted

February 6, 2024

Record last verified: 2024-10

Data Sharing

IPD Sharing
Will share

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.

Locations