A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer

NCT05908734 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: CR10932361186372PANSC20022022-501452-29-00
• Study Type: interventional
• Target: 71
• Locations: 9 countries
• Sites: 43

Brief Summary

The purpose of this study is to identify the recommended Phase 2 (combination) dose (RP2CD) of the amivantamab and cetrelimab 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 combination at the selected RP2CD in participants with NSCLC characterized on the basis of epidermal growth factor receptor (EGFR) and Programmed-cell death Ligand (PD-L)1 status, in the 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 3 months

• 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, hematological toxicity, pulmonary toxicity, liver enzyme elevation, treatment delay greater than (\>) 28 days due to unresolved toxicity, or immune-related toxicity requiring the use of therapies in excess of corticosteroids.

  Up to 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 as per investigator assessment.

  Up to 2 years 3 months

Secondary Outcomes (6)

• Phase 1 and Phase 2: Number of Participants with AEs by Severity

  Up to 2 years 3 months

• Phase 1 and Phase 2: Number of Participants with Abnormalities in Clinical Laboratory Parameters

  Up to 2 years 3 months

• Phase 2 : Duration of Response (DoR)

  Up to 2 years 3 months

• Phase 2: Disease Control Rate (DCR)

  Up to 2 years 3 months

• Phase 2: Progression Free Survival (PFS)

  Up to 2 years 3 months

Study Arms (2)

Phase 1 (Combination Dose Selection)

EXPERIMENTAL

Participants will receive amivantamab low dose or high dose intravenous (IV) infusion based on body weight from Cycle 1 Day 1, Day 2, and subsequently Day 8, Day 15, and Day 22 and then every 2 weeks from Cycle 2 in combination with cetrelimab IV infusion from Cycle 1 Day 2 (after the Day 2 infusion of amivantamab). Cetrelimab treatment duration will be limited to a maximum of 24 months. 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 who continue to benefit from study treatment(s), as determined by their investigator, may continue to receive access to study treatment(s) within the study by transferring to a long term extension (LTE) phase.

Drug: Cetrelimab; Drug: Amivantamab

Phase 2 (Dose Expansion)

EXPERIMENTAL

Participants will receive amivantamab in combination with cetrelimab in Cohorts A and B at the RP2CD determined by the SET in Phase 1. Participants will continue study treatment until disease progression, unacceptable toxicity, or until another criterion for discontinuation of study treatment is met. Cetrelimab treatment duration will be limited to a maximum of 24 months. Participants who continue to benefit from study treatment(s), as determined by their investigator, may continue to receive access to study treatment(s) within the study by transferring to an LTE phase.

Drug: Cetrelimab; Drug: Amivantamab

Interventions

Cetrelimab DRUG

Cetrelimab will be administered as IV infusion.

Also known as: JNJ-63723283

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:

• Participant must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) (any histology), and must have metastatic NSCLC at the time of enrollment: Phase 1 (Combination Dose Selection) Cohort; Metastatic NSCLC progressed on or after standard of care systemic anti-cancer therapy and participant is declining other systemic treatment options, if any;1. Participants without known mutations must have had disease progression on, or have intolerance to, prior platinum-based chemotherapy and PD-(L)1-targeted immunotherapy given concurrently or sequentially, OR 2. Participants with NSCLC characterized by known driver mutations must have had disease progression on, or have intolerance to, appropriate targeted therapies as per local standard of care. Participants may have received prior therapy with amivantamab as long as discontinuation was not due to toxicity. Participants with EGFR mutation must not have had an anti-PD-1/PD-L1 therapy, Phase 2 Expansion Cohorts; Cohort A: Participant's tumor must have an EGFR exon19del or L858R mutation, as determined by local molecular testing, Cohort B: Participants must have tumors lacking known primary driver mutations and must have PD-L1 expression of greater than or equal to (\>=)50 percentage (%), per local testing, and are treatment-naïve in the metastatic setting
• Participant must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, that has not been previously irradiated
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

• Participant has an uncontrolled illness, including but not limited to: a. Uncontrolled diabetes, b. Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy \[participants will be required to complete antibiotics 1 week prior to starting study treatment\] or diagnosed or suspected viral infection), c. Active bleeding diathesis, d. Impaired oxygenation requiring continuous oxygen supplementation, e. Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements
• 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
• Has an active autoimmune disease or a documented history of autoimmune disease that requires systemic steroids or immunosuppressive agents
• Participant has received radiotherapy for palliative purposes less than 14 days prior to the first dose of study treatment
• Participant has a. (or has a history of) leptomeningeal disease (carcinomatous meningitis), b. spinal cord compression not definitively treated with surgery or radiation

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (43)

City of Hope

Duarte, California, 91010, United States

Location

City of Hope Orange County Lennar Foundation Cancer Center

Irvine, California, 92618, United States

Location

Cancer and Blood Specialty Clinic

Los Alamitos, California, 90720, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Providence Oncology and Hematology Care Clinic Westside

Portland, Oregon, 97225, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Fundacao Pio XII

Barretos, 14784 400, Brazil

Location

Cetus Oncologia

Belo Horizonte, 30110 022, Brazil

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

Hospital do Cancer de Londrina

Londrina, 86015 520, Brazil

Location

Hospital Nossa Senhora da Conceicao S A

Porto Alegre, 91350 200, Brazil

Location

Hospital Santa Izabel Santa Casa de Misericordia da Bahia

Salvador, 40050-410, Brazil

Location

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, 01509 900, Brazil

Location

European Institute of Oncology

Milan, 20141, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Aou San Luigi Gonzaga

Orbassano, 10043, Italy

Location

Centro Ricerche Cliniche di Verona S r l

Verona, 37134, Italy

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Hospital Umum Sarawak

Kuching, 93586, Malaysia

Location

INSTYTUT GENETYKI I IMMUNOLOGII GENIM Sp z o o

Lublin, 20 609, Poland

Location

Wielkopolskie Centrum Pulmonologii i Torakochirurgii im. Eugenii i Janusza Zeylandow

Poznan, 60 569, Poland

Location

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy

Warsaw, 02 781, Poland

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hosp. Gral. Univ. de Alicante

Alicante, 03010, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp. Univ. Quiron Dexeus

Barcelona, 8028, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Virgen Macarena

Seville, 41009, Spain

Location

Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Adana City Hospital

Adana, 01170, Turkey (Türkiye)

Location

Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi

Ankara, 06200, Turkey (Türkiye)

Location

Ankara Bilkent Sehir Hastanesi

Ankara, 06800, Turkey (Türkiye)

Location

Bakirkoy Sadi Konuk Training and Research Hospital

Istanbul, 34147, Turkey (Türkiye)

Location

Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi

Istanbul, 34722, Turkey (Türkiye)

Location

Medicana International Izmir

Izmir, 35170, Turkey (Türkiye)

Location

Sakarya Universitesi Egitim Ve Arastırma Hastanesi

Sakarya, 54100, Turkey (Türkiye)

Location

Imperial College London and Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

Location

Freeman Hospital

Newcastle, NE7 7DN, United Kingdom

Location

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

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: June 6, 2023
• First Posted: June 18, 2023
• Study Start: May 18, 2023
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

MY (2); PL (3); IT (4); TU (7); US (7); BR (8); KR (3); ES (6); GB (3)