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A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark)

Primary Purpose

Carcinoma, Non-Small-Cell Lung

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Capmatinib
Amivantamab
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung

Eligibility Criteria

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

Inclusion Criteria:

  • Previously diagnosed with histologically or cytologically confirmed unresectable Stage IV (metastatic) non-small cell lung cancer (NSCLC) (any histology)
  • May have: definitively, locally treated brain metastases that are clinically stable and asymptomatic for greater than (>) 2 weeks and who are off or receiving low-dose corticosteroid treatment (less than or equal to [<=]10 milligrams (mg) prednisone or equivalent) for at least 2 weeks prior to start of study treatment
  • May have a prior malignancy (other than the disease under study) the natural history or treatment of which is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study

Exclusion Criteria:

  • Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
  • Participant has impairment of the gastrointestinal function that could affect absorption of capmatinib or is unable or unwilling to swallow tablets
  • Participant has symptomatic central nervous system (CNS) metastases which are neurologically unstable or have required increasing doses of steroids >10 mg prednisone or equivalent within the 2 weeks prior to study entry to manage CNS symptoms
  • Participant has uncontrolled tumor-related pain: Symptomatic lesions amenable to palliative radiotherapy (example, bone metastases, or metastases causing nerve impingement) should be treated more than 7 days prior to the administration of the first study treatment

Sites / Locations

  • The Oncology Institute of Hope and Innovation
  • Virginia Cancer SpecialistsRecruiting
  • Seoul National University HospitalRecruiting
  • Severance Hospital, Yonsei University Health SystemRecruiting
  • Asan Medical CenterRecruiting
  • Ankara Bilkent City HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1 (Combination Dose Selection)

Phase 2 (Dose Expansion)

Arm Description

Participants will receive capmatinib 400 milligrams (mg) orally twice daily from Cycle 1 Day 1, in combination with amivantamab 700 mg intravenous (IV) infusion (for body weight less than 80 kilograms [kg]) or 1050 mg IV infusion (for body weight greater than or equal to 80 kg) once weekly from Cycle 1 Day 1 for 4 weeks and then every 2 weeks from Week 5 (Cycle 2; each cycle of 28 days). Doses will be escalated or de-escalated based on the dose limiting toxicities (DLTs) and the recommended Phase 2 combination dose (RP2CD) will be determined by the study evaluation team (SET).

Participants with mesenchymal-epithelial transition (MET) exon 14 skipping mutation who are treatment naïve (Cohort 1A), who have received prior therapy (Cohort 1B), or participants with MET amplification who have received prior therapy (Cohort 1C) will receive capmatinib in combination with amivantamab at the RP2CD determined by the SET in Phase 1.

Outcomes

Primary Outcome Measures

Phase 1: Number of Participants with Adverse events (AEs) by Severity
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Phase 1: Number of Participants with Dose Limiting Toxicities (DLTs)
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, hematologic toxicity, pulmonary toxicity, liver enzyme elevation, or treatment delay greater than (>) 28 days due to unresolved toxicity.
Phase 2: Objective Response Rate
ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcome Measures

Phase 1: Number of Participants with AEs by Severity
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. Severity will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Phase 1: Number of Participants with Abnormalities in Clinical Laboratory Parameters
Number of participants with abnormalities in clinical laboratory parameters (serum chemistry, hematology, coagulation, serology, and urinalysis) will be reported.
Phase 2 : Duration of Response (DoR)
DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death from any case, whichever comes first, for participants who have PR or CR.
Phase 2: Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieve a PR, CR, or stable disease using RECIST version 1.1.
Phase 2: Progression Free Survival (PFS)
PFS is defined as the time from first dose date until the date of disease progression or death, whichever comes first, based on investigator assessment using RECIST version 1.1
Phase 2: Overall Survival (OS)
OS is defined as the time from the date of administration of the first study treatment until the date of death due to any cause.
Phase 2: Time to Subsequent Therapy (TTST)
TTST is defined as the time from the date of administration of the first study treatment to the start date of the subsequent anticancer therapy following study treatment discontinuation, or death, whichever comes first.
Phase 2 (Cohort 1A): Change from Baseline in Health-related Quality of Life in (HRQoL) as Assessed by European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score
EORTC-QLQ-C30 is a self-administered, 30-item questionnaire developed to assess the HRQoL of cancer participants.
Phase 2 (Cohort 1A): HRQoL as Assessed by Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ) Scale Score
NSCLC-SAQ assesses patient-reported symptom severity associated with NSCLC.
Phase 2 (Cohort 1A): HRQoL as Assessed by EuroQol 5-Dimension 5-Level (EQ-5D-5L) Scale Score
EQ-5D-5L is a self-administered, standardized measure of health status.
Phase 2 (Cohort 1A): HRQoL as Assessed by Patient-reported Outcomes Measurement Information System Short Form Version 2.0 - Physical Function 8c (PROMIS PF 8c) Scale Score
PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It assesses activities of daily living, mobility, and global impact of physical functioning.

Full Information

First Posted
August 3, 2022
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05488314
Brief Title
A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer
Acronym
METalmark
Official Title
A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 13, 2022 (Actual)
Primary Completion Date
December 27, 2024 (Anticipated)
Study Completion Date
September 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

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

5. Study Description

Brief Summary
The purpose of this study is to identify the recommended Phase 2 combination dose (RP2CD[s]) of the amivantamab and capmatinib combination therapy in participants with non-small cell lung cancer (NSCLC) in Phase 1 (combination dose selection), and to evaluate the antitumor effect of the amivantamab and capmatinib combination therapy in mesenchymal-epithelial transition (MET) exon 14 skipping mutation and MET amplified NSCLC, when administered at the selected RP2CD(s) in Phase 2 (expansion).
Detailed Description
Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer related deaths worldwide. It is a heterogenous disease and is broadly classified as non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). This study will combine the 2 mesenchymal-epithelial transition (MET) inhibitors, amivantamab and capmatinib, which have different mechanisms of MET inhibition and, as monotherapies, have demonstrated clinical activity in MET driven NSCLC. Amivantamab is a bispecific antibody that targets both the epidermal growth factor receptor (EGFR) and MET extracellular ligand binding domains and inhibits ligand driven signaling. Capmatinib is a selective, oral MET tyrosine kinase inhibitor (TKI) that inhibits the MET downstream signaling pathway and thereby inhibits tumor growth and progression. The primary hypothesis of the study is that amivantamab and capmatinib can be safely administered as a combination therapy, with a tolerable safety profile (Phase 1), and the combination of amivantamab and capmatinib will demonstrate clinically significant anti-tumor activity for participants with NSCLC harboring MET exon 14 skipping mutations or MET amplification (Phase 2). The study will include a screening period, a treatment period , and a post-treatment follow-up period. The overall duration of the study will be up to 2 years 1 month.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
161 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 (Combination Dose Selection)
Arm Type
Experimental
Arm Description
Participants will receive capmatinib 400 milligrams (mg) orally twice daily from Cycle 1 Day 1, in combination with amivantamab 700 mg intravenous (IV) infusion (for body weight less than 80 kilograms [kg]) or 1050 mg IV infusion (for body weight greater than or equal to 80 kg) once weekly from Cycle 1 Day 1 for 4 weeks and then every 2 weeks from Week 5 (Cycle 2; each cycle of 28 days). Doses will be escalated or de-escalated based on the dose limiting toxicities (DLTs) and the recommended Phase 2 combination dose (RP2CD) will be determined by the study evaluation team (SET).
Arm Title
Phase 2 (Dose Expansion)
Arm Type
Experimental
Arm Description
Participants with mesenchymal-epithelial transition (MET) exon 14 skipping mutation who are treatment naïve (Cohort 1A), who have received prior therapy (Cohort 1B), or participants with MET amplification who have received prior therapy (Cohort 1C) will receive capmatinib in combination with amivantamab at the RP2CD determined by the SET in Phase 1.
Intervention Type
Drug
Intervention Name(s)
Capmatinib
Intervention Description
Capmatinib will be administered orally.
Intervention Type
Drug
Intervention Name(s)
Amivantamab
Other Intervention Name(s)
JNJ-61186372
Intervention Description
Amivantamab will be administered as IV infusion.
Primary Outcome Measure Information:
Title
Phase 1: Number of Participants with Adverse events (AEs) by Severity
Description
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Time Frame
Up to 2 years 1 month
Title
Phase 1: Number of Participants with Dose Limiting Toxicities (DLTs)
Description
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, hematologic toxicity, pulmonary toxicity, liver enzyme elevation, or treatment delay greater than (>) 28 days due to unresolved toxicity.
Time Frame
Cycle 1 (Day 1 through Day 28)
Title
Phase 2: Objective Response Rate
Description
ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time Frame
Up to 2 years 1 month
Secondary Outcome Measure Information:
Title
Phase 1: Number of Participants with AEs by Severity
Description
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. Severity will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Time Frame
Up to 2 years 1 month
Title
Phase 1: Number of Participants with Abnormalities in Clinical Laboratory Parameters
Description
Number of participants with abnormalities in clinical laboratory parameters (serum chemistry, hematology, coagulation, serology, and urinalysis) will be reported.
Time Frame
Up to 2 years 1 month
Title
Phase 2 : Duration of Response (DoR)
Description
DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death from any case, whichever comes first, for participants who have PR or CR.
Time Frame
Up to 2 years 1 month
Title
Phase 2: Disease Control Rate (DCR)
Description
DCR is defined as the percentage of participants who achieve a PR, CR, or stable disease using RECIST version 1.1.
Time Frame
Up to 2 years 1 month
Title
Phase 2: Progression Free Survival (PFS)
Description
PFS is defined as the time from first dose date until the date of disease progression or death, whichever comes first, based on investigator assessment using RECIST version 1.1
Time Frame
Up to 2 years 1 month
Title
Phase 2: Overall Survival (OS)
Description
OS is defined as the time from the date of administration of the first study treatment until the date of death due to any cause.
Time Frame
Up to 2 years 1 month
Title
Phase 2: Time to Subsequent Therapy (TTST)
Description
TTST is defined as the time from the date of administration of the first study treatment to the start date of the subsequent anticancer therapy following study treatment discontinuation, or death, whichever comes first.
Time Frame
Up to 2 years 1 month
Title
Phase 2 (Cohort 1A): Change from Baseline in Health-related Quality of Life in (HRQoL) as Assessed by European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score
Description
EORTC-QLQ-C30 is a self-administered, 30-item questionnaire developed to assess the HRQoL of cancer participants.
Time Frame
Baseline up to 2 years 1 month
Title
Phase 2 (Cohort 1A): HRQoL as Assessed by Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ) Scale Score
Description
NSCLC-SAQ assesses patient-reported symptom severity associated with NSCLC.
Time Frame
Up to 2 years 1 month
Title
Phase 2 (Cohort 1A): HRQoL as Assessed by EuroQol 5-Dimension 5-Level (EQ-5D-5L) Scale Score
Description
EQ-5D-5L is a self-administered, standardized measure of health status.
Time Frame
Up to 2 years 1 month
Title
Phase 2 (Cohort 1A): HRQoL as Assessed by Patient-reported Outcomes Measurement Information System Short Form Version 2.0 - Physical Function 8c (PROMIS PF 8c) Scale Score
Description
PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It assesses activities of daily living, mobility, and global impact of physical functioning.
Time Frame
Up to 2 years 1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Previously diagnosed with histologically or cytologically confirmed unresectable Stage IV (metastatic) non-small cell lung cancer (NSCLC) (any histology) May have: definitively, locally treated brain metastases that are clinically stable and asymptomatic for greater than (>) 2 weeks and who are off or receiving low-dose corticosteroid treatment (less than or equal to [<=]10 milligrams (mg) prednisone or equivalent) for at least 2 weeks prior to start of study treatment May have a prior malignancy (other than the disease under study) the natural history or treatment of which is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s) Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study Exclusion Criteria: Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening Participant has impairment of the gastrointestinal function that could affect absorption of capmatinib or is unable or unwilling to swallow tablets Participant has symptomatic central nervous system (CNS) metastases which are neurologically unstable or have required increasing doses of steroids >10 mg prednisone or equivalent within the 2 weeks prior to study entry to manage CNS symptoms Participant has uncontrolled tumor-related pain: Symptomatic lesions amenable to palliative radiotherapy (example, bone metastases, or metastases causing nerve impingement) should be treated more than 7 days prior to the administration of the first study treatment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Contact
Phone
844-434-4210
Email
Participate-In-This-Study@its.jnj.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
The Oncology Institute of Hope and Innovation
City
Cerritos
State/Province
California
ZIP/Postal Code
90703
Country
United States
Individual Site Status
Completed
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Ankara Bilkent City Hospital
City
Ankara
ZIP/Postal Code
06800
Country
Turkey
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer

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