NCT04139317

Brief Summary

The purpose was to evaluate the efficacy and safety of the combination of capmatinib with pembrolizumab compared to pembrolizumab alone as first-line treatment for subjects with locally advanced or metastatic NSCLC who have PD-L1 expression ≥ 50% and have no EGFR mutation or ALK rearrangement. Capmatinib has demonstrated immunomodulatory activities when combined with an anti-PD1 antibody in preclinical tumor models irrespective of MET dysregulation. The combination of capmatinib with checkpoint inhibitors has been established to be tolerable and could provide additional clinical benefit to the subjects.

Trial Health

68
Monitor

Trial Health Score

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

Enrollment
76

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2020

Typical duration for phase_2

Geographic Reach
16 countries

36 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

October 14, 2019

Completed
11 days until next milestone

First Posted

Study publicly available on registry

October 25, 2019

Completed
3 months until next milestone

Study Start

First participant enrolled

January 22, 2020

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 14, 2022

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 7, 2023

Completed
1 year until next milestone

Results Posted

Study results publicly available

February 8, 2024

Completed
Last Updated

October 9, 2024

Status Verified

October 1, 2024

Enrollment Period

2 years

First QC Date

October 14, 2019

Results QC Date

January 15, 2024

Last Update Submit

October 7, 2024

Conditions

Keywords

capmatinibpembrolizumabNSCLCPD-L1EGFRALKMET,squamousnon-squamous

Outcome Measures

Primary Outcomes (1)

  • Progression-Free Survival (PFS) by Investigator Assessment as Per RECIST 1.1

    PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. Tumor response was based on investigator assessment per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment, the start of a subsequent anti-neoplastic therapy (if any) or the date of sponsor's decision to discontinue capmatinib (applicable only to subjects on the combination arm). Due to the discontinuation of one of the investigational drugs (capmatinib) in all subjects in the combination arm, PFS was censored on the 21-Jan-2021 or the last adequate tumor assessment prior to that date for the capmatinib plus pembrolizumab arm. PFS was analyzed using Kaplan-Meier estimates.

    Up to 1.3 years

Secondary Outcomes (11)

  • Overall Response Rate (ORR) by Investigator Assessment as Per RECIST 1.1

    Up to 1.3 years

  • Disease Control Rate (DCR) by Investigator Assessment as Per RECIST 1.1

    Up to 1.3 years

  • Time to Response (TTR) by Investigator Assessment as Per RECIST 1.1

    Up to 1.3 years

  • Duration of Response (DOR) by Investigator Assessment as Per RECIST 1.1

    Up to 1.3 years

  • Overall Survival (OS)

    Up to 2.1 years

  • +6 more secondary outcomes

Study Arms (2)

Capmatinib 400mg BID + pembrolizumab 200mg Q3W

EXPERIMENTAL

Capmatinib (INC280) 400 mg orally twice daily (BID) in combination with pembrolizumab 200 mg intravenously every 3 weeks (Q3W)

Drug: CapmatinibBiological: Pembrolizumab

Pembrolizumab 200mg Q3W

ACTIVE COMPARATOR

Pembrolizumab 200 mg intravenously every 3 weeks (Q3W)

Biological: Pembrolizumab

Interventions

INC280 tablets were administered orally at 400 mg on a continuous twice daily (BID) dosing schedule, from Day 1 until Day 21 of each 21-day cycle.

Also known as: INC280
Capmatinib 400mg BID + pembrolizumab 200mg Q3W
PembrolizumabBIOLOGICAL

Pembrolizumab was administered by intravenous infusion at 200 mg once every 3 weeks (Q3W).

Also known as: Keytruda®, MK-3475
Capmatinib 400mg BID + pembrolizumab 200mg Q3WPembrolizumab 200mg Q3W

Eligibility Criteria

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

You may qualify if:

  • Histologically confirmed and documented locally advanced stage III (not candidates for surgical resection or definitive chemo-radiation) or stage IV (metastatic) NSCLC (per AJCC/IASLC v.8) for treatment in the first-line setting
  • Histologically or cytologically confirmed diagnosis of NSCLC that is both EGFR wild type status and ALK- negative rearrangement statu
  • Have an archival tumor sample or newly obtained tumor biopsy with high PD-L1 expression (TPS ≥ 50%)
  • ECOG performance status score ≤ 1
  • Have at least 1 measurable lesion by RECIST 1.1
  • Have adequate organ function

You may not qualify if:

  • Prior treatment with a MET inhibitor or HGF-targeting therapy
  • Prior immunotherapy (e.g. anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways)
  • Have untreated symptomatic central nervous system (CNS) metastases
  • Clinically significant, uncontrolled heart diseases
  • Prior palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study treatment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (36)

Novartis Investigative Site

Wollongong, New South Wales, 2500, Australia

Location

Novartis Investigative Site

North Adelaide, South Australia, 5006, Australia

Location

Novartis Investigative Site

Shepparton, Victoria, 3630, Australia

Location

Novartis Investigative Site

Yvoir, 5530, Belgium

Location

Novartis Investigative Site

Québec, Quebec, GIV 4G5, Canada

Location

Novartis Investigative Site

Ostrava Vitkovice, 703 84, Czechia

Location

Novartis Investigative Site

Lille, 59000, France

Location

Novartis Investigative Site

Strasbourg, 67091, France

Location

Novartis Investigative Site

Toulouse, 31400, France

Location

Novartis Investigative Site

Berlin, 14165, Germany

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Athens, 11526, Greece

Location

Novartis Investigative Site

Thessaloniki, 57001, Greece

Location

Novartis Investigative Site

Shatin New Territories, Hong Kong, Hong Kong

Location

Novartis Investigative Site

Mumbai, Maharashtra, 401107, India

Location

Novartis Investigative Site

Kolkata, West Bengal, 700160, India

Location

Novartis Investigative Site

Delhi, 110 085, India

Location

Novartis Investigative Site

Ancona, AN, 60126, Italy

Location

Novartis Investigative Site

Aviano, PN, 33081, Italy

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 466 8560, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa, 236 0051, Japan

Location

Novartis Investigative Site

Kuching, Sarawak, 93586, Malaysia

Location

Novartis Investigative Site

Kuala Lumpur, 59100, Malaysia

Location

Novartis Investigative Site

Amersfoort, 3813 TZ, Netherlands

Location

Novartis Investigative Site

Breda, 4819 EV, Netherlands

Location

Novartis Investigative Site

Zwolle, 8025 AB, Netherlands

Location

Novartis Investigative Site

Badalona, Catalonia, 08916, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Barcelona, 08041, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Changhua, 50006, Taiwan

Location

Novartis Investigative Site

Taichung, 40705, Taiwan

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10400, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

capmatinibpembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 14, 2019

First Posted

October 25, 2019

Study Start

January 22, 2020

Primary Completion

January 14, 2022

Study Completion

February 7, 2023

Last Updated

October 9, 2024

Results First Posted

February 8, 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