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

• ClinicalTrials.gov Identifier: NCT05488314
• Recruitment Status: Recruiting
• First Posted: August 4, 2022
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: August 3, 2022
• First Posted Date: August 4, 2022
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: December 13, 2022
• Estimated Primary Completion Date: December 27, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 3, 2022)

• Phase 1: Number of Participants with Adverse events (AEs) by Severity [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Cycle 1 (Day 1 through Day 28) ]
  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 [ Time Frame: Up to 2 years 1 month ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 17, 2023)

• Phase 1: Number of Participants with AEs by Severity [ Time Frame: Up to 2 years 1 month ]
  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 [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Up to 2 years 1 month ]
  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 [ Time Frame: Baseline up to 2 years 1 month ]
  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 [ Time Frame: Up to 2 years 1 month ]
  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 [ Time Frame: Up to 2 years 1 month ]
  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 [ Time Frame: Up to 2 years 1 month ]
  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.

Original Secondary Outcome Measures (submitted: August 3, 2022)

• Phase 1: Number of Participants with AEs by Severity [ Time Frame: Up to 2 years 1 month ]
  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 [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Up to 2 years 1 month ]
  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) [ Time Frame: Up to 2 years 1 month ]
  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 [ Time Frame: Baseline up to 2 years 1 month ]
  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 [ Time Frame: Up to 2 years 1 month ]
  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 [ Time Frame: Up to 2 years 1 month ]
  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 [ Time Frame: Up to 2 years 1 month ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer
• 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
• 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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• Drug: Capmatinib
  Capmatinib will be administered orally.
• Drug: Amivantamab
  Amivantamab will be administered as IV infusion.
  Other Name: JNJ-61186372

Study Arms

• Experimental: Phase 1 (Combination Dose Selection)
  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).
  Interventions:

  • Drug: Capmatinib
  • Drug: Amivantamab
• Experimental: Phase 2 (Dose Expansion)
  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.
  Interventions:

  • Drug: Capmatinib
  • Drug: Amivantamab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 12, 2022): 161
• Original Estimated Enrollment (submitted: August 3, 2022): 147
• Estimated Study Completion Date: August 22, 2026
• Estimated Primary Completion Date: December 27, 2024 (Final data collection date for primary outcome measure)

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 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Brazil, Canada, China, France, Germany, Italy, Japan, Korea, Republic of, Poland, Spain, Turkey, United Kingdom, United States
• Removed Location Countries: Puerto Rico

Administrative Information

• NCT Number: NCT05488314
• Other Study ID Numbers: CR109260; 61186372PANSC2001 ( Other Identifier: Janssen Research & Development, LLC ); 2022-000485-18 ( EudraCT Number ); 2022-500729-34-00 ( Registry Identifier: EUCT number ); 2023-508256-19-00 ( Registry Identifier: EUCT number )
• Has Data Monitoring Committee: No

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

• Plan to Share IPD: Yes
• 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
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024