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Safety and Efficacy of Capmatinib (INC280) Plus Pembrolizumab vs Pembrolizumab Alone in NSCLC With PD-L1≥ 50%

Primary Purpose

Non-small Cell Lung Cancer (NSCLC)

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Capmatinib
Pembrolizumab
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer (NSCLC) focused on measuring capmatinib, pembrolizumab, NSCLC, PD-L1, EGFR, ALK, MET, squamous, non-squamous

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Combination arm

monotherapy

Arm Description

Capmatinib 400 mg twice a day Pembrolizumab 200mg every 3 weeks

Pembrolizumab 200mg every 3 weeks

Outcomes

Primary Outcome Measures

Progression-free survival (PFS) based on local investigator assessment as per RECIST 1.1
Progression free survival is defined as the time from randomization to the date of the first documented radiological progression using RECIST 1.1(Response evaluation criteria in solid tumor) or death due to any cause

Secondary Outcome Measures

Objective response rate (ORR) based on local investigator assessment as per RECIST 1.1
ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1
Disease control rate (DCR) based on local investigator assessment as per RECIST 1.1
Disease control rate is defined as the proportion of patients with complete response (CR) or partial response (PR) or subjects with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria
Time-to-response (TTR) based on local investigator assessment as per RECIST 1.1
Time to response (TTR) is defined as duration of time between the date of randomization and the date of first documented response of either CR or PR, according to RECIST 1.1 criteria
Duration of response (DOR) based on local investigator assessment as per RECIST 1.1
Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death, according to RECIST 1.1 criteria
Overall survival (OS)
Overall survival is defined as the time from date of randomization to date of death due to any cause
Antidrug antibodies (ADA) of pembrolizumab
Concentration/presence of ADA to be measured
AUC of capmatinib derived from plasma capmatinib concentration
AUC of capmatinib is defined as area under the plasma concentration-time curve determined using non-compartmental methods.
Ctrough of pembrolizumab derived from serum pembrolizumab concentration
Ctrough of pembrolizumab is defined as the measured serum concentration at the end of a dosing interval at steady state
Cmax of capmatinib derived from plasma capmatinib concentration
Cmax of capmatinib is defined as the maximum observed plasma concentration after single dose administration
Tmax of capmatinib derived from plasma capmatinib concentration
Tmax of capmatinib is defined as the time to reach maximum plasma concentration after single dose administration
Incidence of adverse events
Incidence of adverse events is defined as number of participants with adverse events (AEs), serious adverse events (SAEs) and AEs leading to dose interruption, dose reduction and dose discontinuation.

Full Information

First Posted
October 14, 2019
Last Updated
February 16, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04139317
Brief Title
Safety and Efficacy of Capmatinib (INC280) Plus Pembrolizumab vs Pembrolizumab Alone in NSCLC With PD-L1≥ 50%
Official Title
A Randomized, Open Label, Multicenter Phase II Study Evaluating the Efficacy and Safety of Capmatinib (INC280) Plus Pembrolizumab Versus Pembrolizumab Alone as First Line Treatment for Locally Advanced or Metastatic Non-small Cell Lung Cancer With PD-L1≥ 50%
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision to terminate due to the lack of tolerability observed in patients treated with capmatinib and pembrolizumab in the combination arm as compared to patients treated with pembrolizumab alone in the pembrolizumab single agent arm
Study Start Date
January 22, 2020 (Actual)
Primary Completion Date
January 14, 2022 (Actual)
Study Completion Date
February 7, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose is 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer (NSCLC)
Keywords
capmatinib, pembrolizumab, NSCLC, PD-L1, EGFR, ALK, MET, squamous, non-squamous

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Combination arm
Arm Type
Experimental
Arm Description
Capmatinib 400 mg twice a day Pembrolizumab 200mg every 3 weeks
Arm Title
monotherapy
Arm Type
Active Comparator
Arm Description
Pembrolizumab 200mg every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Capmatinib
Other Intervention Name(s)
INC280
Intervention Description
Oral tablet
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda®, MK-3475
Intervention Description
IV infusion
Primary Outcome Measure Information:
Title
Progression-free survival (PFS) based on local investigator assessment as per RECIST 1.1
Description
Progression free survival is defined as the time from randomization to the date of the first documented radiological progression using RECIST 1.1(Response evaluation criteria in solid tumor) or death due to any cause
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Objective response rate (ORR) based on local investigator assessment as per RECIST 1.1
Description
ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1
Time Frame
18 months
Title
Disease control rate (DCR) based on local investigator assessment as per RECIST 1.1
Description
Disease control rate is defined as the proportion of patients with complete response (CR) or partial response (PR) or subjects with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria
Time Frame
18 months
Title
Time-to-response (TTR) based on local investigator assessment as per RECIST 1.1
Description
Time to response (TTR) is defined as duration of time between the date of randomization and the date of first documented response of either CR or PR, according to RECIST 1.1 criteria
Time Frame
18 months
Title
Duration of response (DOR) based on local investigator assessment as per RECIST 1.1
Description
Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death, according to RECIST 1.1 criteria
Time Frame
18 months
Title
Overall survival (OS)
Description
Overall survival is defined as the time from date of randomization to date of death due to any cause
Time Frame
18 months
Title
Antidrug antibodies (ADA) of pembrolizumab
Description
Concentration/presence of ADA to be measured
Time Frame
13 months
Title
AUC of capmatinib derived from plasma capmatinib concentration
Description
AUC of capmatinib is defined as area under the plasma concentration-time curve determined using non-compartmental methods.
Time Frame
13 months
Title
Ctrough of pembrolizumab derived from serum pembrolizumab concentration
Description
Ctrough of pembrolizumab is defined as the measured serum concentration at the end of a dosing interval at steady state
Time Frame
13 months
Title
Cmax of capmatinib derived from plasma capmatinib concentration
Description
Cmax of capmatinib is defined as the maximum observed plasma concentration after single dose administration
Time Frame
13 months
Title
Tmax of capmatinib derived from plasma capmatinib concentration
Description
Tmax of capmatinib is defined as the time to reach maximum plasma concentration after single dose administration
Time Frame
13 months
Title
Incidence of adverse events
Description
Incidence of adverse events is defined as number of participants with adverse events (AEs), serious adverse events (SAEs) and AEs leading to dose interruption, dose reduction and dose discontinuation.
Time Frame
19 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 Other protocol-defined inclusion/exclusion criteria may apply.
Facility Information:
Facility Name
Novartis Investigative Site
City
Wollongong
State/Province
New South Wales
ZIP/Postal Code
2500
Country
Australia
Facility Name
Novartis Investigative Site
City
North Adelaide
State/Province
South Australia
ZIP/Postal Code
5006
Country
Australia
Facility Name
Novartis Investigative Site
City
Shepparton
State/Province
Victoria
ZIP/Postal Code
3630
Country
Australia
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Novartis Investigative Site
City
Quebec
ZIP/Postal Code
GIV 4G5
Country
Canada
Facility Name
Novartis Investigative Site
City
Ostrava Vitkovice
ZIP/Postal Code
703 84
Country
Czechia
Facility Name
Novartis Investigative Site
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
Novartis Investigative Site
City
Strasbourg Cedex
ZIP/Postal Code
67091
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse
ZIP/Postal Code
31400
Country
France
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
14165
Country
Germany
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
11526
Country
Greece
Facility Name
Novartis Investigative Site
City
Thessaloniki
ZIP/Postal Code
57001
Country
Greece
Facility Name
Novartis Investigative Site
City
Shatin, New Territories
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
401107
Country
India
Facility Name
Novartis Investigative Site
City
Kolkata
State/Province
West Bengal
ZIP/Postal Code
700160
Country
India
Facility Name
Novartis Investigative Site
City
Delhi
ZIP/Postal Code
110 085
Country
India
Facility Name
Novartis Investigative Site
City
Ancona
State/Province
AN
ZIP/Postal Code
60126
Country
Italy
Facility Name
Novartis Investigative Site
City
Aviano
State/Province
PN
ZIP/Postal Code
33081
Country
Italy
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466 8560
Country
Japan
Facility Name
Novartis Investigative Site
City
Yokohama-city
State/Province
Kanagawa
ZIP/Postal Code
236 0051
Country
Japan
Facility Name
Novartis Investigative Site
City
Kuching
State/Province
Sarawak
ZIP/Postal Code
93586
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Amersfoort
ZIP/Postal Code
3813 TZ
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Breda
ZIP/Postal Code
4819 EV
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Zwolle
ZIP/Postal Code
8025 AB
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Badalona
State/Province
Catalunya
ZIP/Postal Code
08916
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46010
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Novartis Investigative Site
City
Changhua
ZIP/Postal Code
50006
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

Safety and Efficacy of Capmatinib (INC280) Plus Pembrolizumab vs Pembrolizumab Alone in NSCLC With PD-L1≥ 50%

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