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

NCT05488314 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: CR10926061186372PANSC20012022-000485-182023-508256-19-00
• Study Type: interventional
• Target: 57
• Locations: 13 countries
• Sites: 78

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).

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (11)

• Phase 1: Number of Participants with AEs by Severity

  Up to 2 years 1 month

• Phase 1: Number of Participants with Abnormalities in Clinical Laboratory Parameters

  Up to 2 years 1 month

• Phase 2: Duration of Response (DoR)

  Up to 2 years 1 month

• Phase 2: Disease Control Rate (DCR)

  Up to 2 years 1 month

• Phase 2: Progression Free Survival (PFS)

  Up to 2 years 1 month

Study Arms (2)

Phase 1 (Combination Dose Selection)

EXPERIMENTAL

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; Drug: Amivantamab

Phase 2 (Dose Expansion)

EXPERIMENTAL

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; Drug: Amivantamab

Interventions

Capmatinib DRUG

Capmatinib will be administered orally.

Phase 1 (Combination Dose Selection); Phase 2 (Dose Expansion)

Amivantamab DRUG

Amivantamab will be administered as IV infusion.

Also known as: JNJ-61186372

Phase 1 (Combination Dose Selection); Phase 2 (Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (78)

University of Alabama at Birmingham, Comprehensive Cancer Center

Birmingham, Alabama, 35233, United States

Location

The Oncology Institute of Hope and Innovation

Cerritos, California, 90703, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Montefiore Einstein Center for Cancer Care

The Bronx, New York, 10467, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

PERSONAL Oncologia de Precisao e Personalizada

Belo Horizonte, 30130-090, Brazil

Location

CIONC Centro Integrado de Oncologia de Curitiba

Curitiba, 80810 050, Brazil

Location

UPCO Unidade de Pesquisa Clinica em Oncologia

Pelotas, 96020 080, Brazil

Location

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS

Porto Alegre, 90610-000, Brazil

Location

Oncoclinicas Rio de Janeiro S A

Rio de Janeiro, 22 250 905, Brazil

Location

Instituto D Or de Pesquisa e Ensino IDOR

Rio de Janeiro, 22281 100, Brazil

Location

Nucleo de Oncologia da Bahia

Salvador, 40170 110, Brazil

Location

Sociedade Beneficente de Senhoras Hospital Sirio Libanes

São Paulo, 01308 901, Brazil

Location

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, 01509 900, Brazil

Location

The Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, M5G 1Z5, Canada

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Sichuan Cancer Hospital

Chengdu, 610041, China

Location

West China Hospital Sichuan University

Chengdu, 610041, China

Location

Chongqing University Cancer Hospital

Chongqing, 400030, China

Location

The First Affiliated Hospital Sun Yat sen University

Guangzhou, 510060, China

Location

Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, 310009, China

Location

Sir Run Run Shaw Hospital Zhejiang University School of Medicine

Hangzhou, 310016, China

Location

Huizhou Municipal Central Hospital

Huizhou, 516001, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

Shengjing Hospital Of China Medical University

Shenyang, 110055, China

Location

The First Affiliated Hospital of Xian Jiaotong University

Xi'an, 710061, China

Location

Yantai Yuhuangding Hospital

Yantai, 264000, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

Institute Coeur Poumon

Lille, 59000, France

Location

CHU de la Timone

Marseille, 13005, France

Location

Institut de cancerologie de l'ouest

Saint-Herblain, 44805, France

Location

Nouvel Hopital Civil - CHU Strasbourg

Strasbourg, 67091, France

Location

Charite Universitaetsmedizin Berlin

Berlin, 12203, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09116, Germany

Location

Universitaetsklinikum Koeln

Cologne, 50937, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, 01307, Germany

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

Universitaetsklinikum Muenster

Münster, 48149, Germany

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Fondazione G Pascale Istituto Nazionale Tumori IRCCS

Naples, 80131, Italy

Location

Istituto Oncologico Veneto - IRCCS

Padova, 35128, Italy

Location

Ospedale S. Maria Delle Croci

Ravenna, 48121, Italy

Location

Istituto Nazionale Tumori Regina Elena

Rome, 00128, Italy

Location

National Hospital Organization Nagoya Medical Center

Nagoya, 460-0001, Japan

Location

Shizuoka Cancer Center

Sunto Gun, 411 8777, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135 8550, Japan

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80 214, Poland

Location

INSTYTUT GENETYKI I IMMUNOLOGII GENIM Sp z o o

Lublin, 20 609, Poland

Location

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy

Warsaw, 02 781, Poland

Location

Chungbuk National University Hospital

Cheongju-si, 28644, South Korea

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hosp Univ A Coruna

A Coruña, 15006, Spain

Location

Hosp. Gral. Univ. de Alicante

Alicante, 03010, Spain

Location

Hosp. Del Mar

Barcelona, 08003, Spain

Location

Hosp. Univ. Quiron Dexeus

Barcelona, 08028, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Univ. La Paz

Madrid, 28046, Spain

Location

Hosp. Virgen Macarena

Seville, 41009, Spain

Location

Hosp. Clinico Univ. de Valencia

Valencia, 46010, Spain

Location

Gazi University Hospital

Ankara, 06560, Turkey (Türkiye)

Location

Ankara Bilkent City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Ankara Bilkent Sehir Hastanesi

Çankaya, 06800, Turkey (Türkiye)

Location

University College London Hospitals Nhs Foundation Trust

London, NW1 2PG, United Kingdom

Location

Imperial College London and Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

Location

Sir Bobby Robson Cancer Trials Research Centre

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

capmatinib; amivantamab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2022
• First Posted: August 4, 2022
• Study Start: December 13, 2022
• Primary Completion (Estimated): June 9, 2026
• Study Completion (Estimated): April 28, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

IT (6); BR (9); CN (14); JP (3); KR (8); DE (6); US (5); CA (2); PL (3); FR (4); ES (11); TU (3); GB (4)