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

A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Capmatinib; Drug: Amivantamab

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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil, 30130-090
    • PERSONAL Oncologia de Precisao e Personalizada
  • Curitiba, Brazil, 80810 050
    • CIONC Centro Integrado de Oncologia de Curitiba
  • Pelotas, Brazil, 96020 080
    • UPCO Unidade de Pesquisa Clinica em Oncologia
  • Porto Alegre, Brazil, 90610-000
    • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
  • Rio de Janeiro, Brazil, 22 250 905
    • Oncoclinicas Rio de Janeiro S A
  • Rio de Janeiro, Brazil, 22281 100
    • Instituto D Or de Pesquisa e Ensino IDOR
  • Salvador, Brazil, 40170 110
    • Nucleo de Oncologia da Bahia
  • São Paulo, Brazil, 01308 901
    • Sociedade Beneficente de Senhoras Hospital Sirio Libanes
  • São Paulo, Brazil, 01509 900
    • Fundacao Antonio Prudente A C Camargo Cancer Center
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Centre University Health Network
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Chengdu, China, 610041
    • Sichuan Cancer Hospital
  • Chengdu, China, 610041
    • West China Hospital Sichuan University
  • Chongqing, China, 400030
    • Chongqing University Cancer Hospital
  • Guangzhou, China, 510060
    • The First Affiliated Hospital Sun Yat sen University
  • Hangzhou, China, 310009
    • Second Affiliated Hospital, School of Medicine, Zhejiang University
  • Hangzhou, China, 310016
    • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
  • Huizhou, China, 516001
    • Huizhou Municipal Central Hospital
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
  • Shenyang, China, 110055
    • Shengjing Hospital of China Medical University
  • Xi'an, China, 710061
    • The First Affiliated Hospital of Xiân Jiaotong University
  • Yantai, China, 264000
    • Yantai Yuhuangding Hospital
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• France
  • Lille, France, 59000
    • Institute Coeur Poumon
  • Marseille, France, 13005
    • CHU de la Timone
  • Saint-Herblain, France, 44805
    • Institut de Cancerologie de L'Ouest
  • Strasbourg, France, 67091
    • Nouvel Hopital Civil - CHU Strasbourg
• Germany
  • Berlin, Germany, 12203
    • Charite Universitaetsmedizin Berlin
  • Chemnitz, Germany, 09116
    • Klinikum Chemnitz gGmbH
  • Cologne, Germany, 50937
    • Universitaetsklinikum Koeln
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • Münster, Germany, 48149
    • Universitaetsklinikum Müenster
• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy, 20162
    • Asst Grande Ospedale Metropolitano Niguarda
  • Naples, Italy, 80131
    • Fondazione G Pascale Istituto Nazionale Tumori IRCCS
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto - IRCCS
  • Ravenna, Italy, 48121
    • Ospedale S. Maria delle Croci
  • Rome, Italy, 00128
    • Istituto Nazionale Tumori Regina Elena
• Japan
  • Nagoya, Japan, 460-0001
    • National Hospital Organization Nagoya Medical Center
  • Sunto Gun, Japan, 411 8777
    • Shizuoka Cancer Center
  • Tokyo, Japan, 135 8550
    • The Cancer Institute Hospital of Jfcr
• Poland
  • Gdansk, Poland, 80 214
    • Uniwersyteckie Centrum Kliniczne
  • Lublin, Poland, 20 609
    • INSTYTUT GENETYKI I IMMUNOLOGII GENIM Sp z o o
  • Warsaw, Poland, 02 781
    • Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
• South Korea
  • Cheongju-si, South Korea, 28644
    • Chungbuk National University Hospital
  • Goyang-si, South Korea, 10408
    • National Cancer Center
  • Incheon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Jeollanam-do, South Korea, 58128
    • Chonnam National University Hwasun Hospital
  • Seongnam, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System
• Spain
  • A Coruña, Spain, 15006
    • Hosp Univ A Coruna
  • Alicante, Spain, 03010
    • Hosp. Gral. Univ. de Alicante
  • Barcelona, Spain, 08028
    • Hosp. Univ. Quiron Dexeus
  • Barcelona, Spain, 08003
    • Hosp. Del Mar
  • Barcelona, Spain, 08036
    • Hosp Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
  • Madrid, Spain, 28040
    • Hosp Univ Fund Jimenez Diaz
  • Seville, Spain, 41009
    • Hosp. Virgen Macarena
  • Valencia, Spain, 46010
    • Hosp. Clinico Univ. de Valencia
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06800
    • Ankara Bilkent City Hospital
  • Ankara, Turkey (Türkiye), 06560
    • Gazi University Hospital
  • Çankaya, Turkey (Türkiye), 06800
    • Ankara Bilkent Şehir Hastanesi
• United Kingdom
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals NHS Foundation Trust
  • London, United Kingdom, W2 1NY
    • Imperial College London and Imperial College Healthcare NHS Trust
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Sir Bobby Robson Cancer Trials Research Centre
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham, Comprehensive Cancer Center
  • California
    • Cerritos, California, United States, 90703
      • The Oncology Institute of Hope and Innovation
    • Los Angeles, California, United States, 90095
      • UCLA
  • New York
    • The Bronx, New York, United States, 10467
      • Montefiore Einstein Center for Cancer Care
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	Drug: Capmatinib; Capmatinib will be administered orally.; Drug: Amivantamab; Amivantamab will be administered as IV infusion.; Other Names: JNJ-61186372
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.	Drug: Capmatinib; Capmatinib will be administered orally.; Drug: Amivantamab; Amivantamab will be administered as IV infusion.; Other Names: JNJ-61186372

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years 1 month
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.	Cycle 1 (Day 1 through Day 28)
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.	Up to 2 years 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years 1 month
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.	Up to 2 years 1 month
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.	Up to 2 years 1 month
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	Up to 2 years 1 month
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.	Up to 2 years 1 month
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.	Up to 2 years 1 month
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.	Baseline up to 2 years 1 month
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.	Up to 2 years 1 month
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.	Up to 2 years 1 month
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.	Up to 2 years 1 month
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.	Up to 2 years 1 month

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2022
• Primary Completion (Estimated): June 9, 2026
• Study Completion (Estimated): April 28, 2027

Study Registration Dates

• First Submitted: August 3, 2022
• First Submitted That Met QC Criteria: August 3, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; amivantamab; capmatinib
• Other Study ID Numbers: CR109260; 61186372PANSC2001 (Other Identifier: Janssen Research & Development, LLC); 2022-000485-18 (EudraCT Number); 2023-508256-19-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No