A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer

NCT ID: NCT04077463

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 701 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-04
• Study Completion Date: 2026-06-03

Brief Summary

The purpose of this study is to confirm the tolerability of recommended Phase 2 dose (RP2D) of Lazertinib (Phase 1), to determine the tolerability and identify the recommended Phase 2 combination dose of Lazertinib when combined with Amivantamab (JNJ-61186372) (Phase 1b), to characterize the safety and tolerability of Lazertinib and Amivantamab combinations at the RP2CD in participants with advanced non-small cell lung cancer (NSCLC) with documented advanced or metastatic epidermal growth factor receptor (EGFR) mutation (Phase 1b expansion cohorts A, B, C, D and E), to estimate the antitumor activity of Lazertinib and Amivantamab combinations at the RP2CD in participants with advanced NSCLC with documented advanced or metastatic EGFR mutation (Phase 1b expansion cohorts A, B, C, and D), to validate the biomarker identified in Phase 1b expansion Cohort D as a predictor of antitumor activity of Lazertinib and Amivantamab combination (Cohort E) or Amivantamab monotherapy (Cohort F) in participants with osimertinib-relapsed, chemotherapy-naïve, EGFR Exon19del or L858R mutated NSCLC, to identify the recommended Phase 2 dose (RP2ChD) of Lazertinib when combined with Amivantamab and standard of care chemotherapy and to determine the tolerability of the Lazertinib, Amivantamab, and platinum-doublet chemotherapy (LACP) combination (Phase 1b LACP combination cohort) and to characterize the safety and tolerability of Lazertinib at the RP2ChD and Amivantamab and standard of care chemotherapy in participants with advanced or metastatic EGFR-mutated NSCLC (Phase 1b LACP combination cohort), to assess 2 potential biomarker strategies to identify participants at increased, or decreased, probability of tumor response with JNJ-61186372 and lazertinib combination in participants with EGFR Exon19del or L858R mutated NSCLC progressed on or after osimertinib (Phase 1b expansion Cohort D).

Detailed Description

Lung cancer is one of the most common types of cancer and is also the most common cause of death from cancer. NSCLC accounts for 85 percent (%) to 90% of lung cancers. Lazertinib is an oral, highly potent, mutant-selective, and irreversible EGFR-tyrosine kinase inhibitor (TKI) targeting both, the T790M mutation and activating EGFR mutations while sparing wild type EGFR. JNJ-61186372 (also referred to as amivantamab), is a low fucose, fully human immunoglobulin G1(IgG1)-based bispecific antibody. As a third generation EGFR-TKI targeting activating EGFR mutations, lazertinib has a distinct mechanism of action from JNJ-61186372, which targets the extracellular domains of both the EGFR and cMet proteins. The distinct mechanisms of action of lazertinib and JNJ-61186372 suggests potential to improve clinical outcomes through the combination of these two molecules. Phase 1 and 1b lazertinib + amivantamab, and Phase 1b LACP combination cohort are divided into 2 periods: screening and treatment period whereas Phase 1b expansion cohorts are divided into 3 periods: screening, treatment, and post-treatment follow up period. Safety assessment will include adverse events (AEs), serious adverse events (SAEs), physical examinations, Eastern Cooperative Oncology Group (ECOG) criteria for performance status, laboratory tests, vital signs, electrocardiograms, chest x-ray, baseline ophthalmologic examination (Phase 1b Expansion Cohorts), echocardiography or multigated acquisition, and concomitant medication usage. The overall duration of the study will be up to 5 years and 2 months.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 (monotherapy dose escalation): Lazertinib

Participants will receive Lazertinib monotherapy orally once daily (QD) in 21-day cycles until documented evidence of disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. The subsequent doses of Lazertinib will be assigned by the Study Evaluation Team (SET) according to the dose escalation strategy by Bayesian logistic regression model (BLRM).

Group Type: EXPERIMENTAL

Lazertinib

Intervention Type: DRUG

Lazertinib will be administered orally.

Phase 1b (combination): Lazertinib and Amivantamab

Participants will receive Lazertinib and Amivantamab, after the safety of RP2D of Lazertinib is confirmed in the Phase 1, in 28-day cycles until documented evidence of disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. This phase will start enrolling participants after the safety of Amivantamab is confirmed in Japanese participants in Study 61186372EDI1001 (NCT02609776).

Group Type: EXPERIMENTAL

Lazertinib

Intervention Type: DRUG

Lazertinib will be administered orally.

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered as an intravenous (IV) infusion.

Phase 1b (combination): Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP)

Participants will receive Lazertinib starting dose administered orally once daily (QD) in combination with Amivantamab, and doses of platinum-based chemotherapy (carboplatin and pemetrexed) per standard of care according to local guidance in a 21-day cycle for 4 cycles followed by maintenance with Lazertinib, Amivantamab and pemetrexed until disease progression or unacceptable toxicities.

Group Type: EXPERIMENTAL

Lazertinib

Intervention Type: DRUG

Lazertinib will be administered orally.

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered as an intravenous (IV) infusion.

Carboplatin

Intervention Type: DRUG

Carboplatin will be administered as IV infusion.

Pemetrexed

Intervention Type: DRUG

Pemetrexed will be administered as IV infusion.

Phase 1b (expansion) Cohort A: Lazertinib and Amivantamab

This cohort A will further characterize the safety, tolerability, and preliminary antitumor activity of Lazertinib and Amivantamab based combinations within specific NSCLC population "who have progressed after osimertinib and subsequent platinum-based chemotherapy, and platinum-based chemotherapy regimen as the last line of therapy prior to study enrollment. Prior use of first or second generation EGFR TKI is allowed if administered prior to osimertinib. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.

Group Type: EXPERIMENTAL

Lazertinib

Intervention Type: DRUG

Lazertinib will be administered orally.

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered as an intravenous (IV) infusion.

Phase 1b (expansion) Cohort B: Lazertinib and Amivantamab

This Cohort B will further characterize the safety, tolerability and preliminary antitumor activity of Lazertinib and JNJ-61186372 combination in participants previously treated with advanced or metastatic NSCLC with documented primary EGFR Exon 20ins activating mutation. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.

Group Type: EXPERIMENTAL

Lazertinib

Intervention Type: DRUG

Lazertinib will be administered orally.

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered as an intravenous (IV) infusion.

Phase 1b (expansion) Cohort C: Lazertinib and Amivantamab

This Cohort C will further characterize the safety, tolerability and preliminary antitumor activity of Lazertinib and JNJ-61186372 combination in participants with uncommon EGFR mutations. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.

Group Type: EXPERIMENTAL

Lazertinib

Intervention Type: DRUG

Lazertinib will be administered orally.

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered as an intravenous (IV) infusion.

Phase 1b (expansion) Cohort D: Lazertinib and Amivantamab

Cohort D will seek to validate one or both potential biomarker strategies (next generation sequencing \[NGS\] and Immunohistochemical \[IHC\]), previously identified in Cohort E of Study 61186372EDI1001, in participants with osimertinib-relapsed, but chemotherapy-naive, EGFR Exon19del or L858R mutated NSCLC. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter.

Group Type: EXPERIMENTAL

Lazertinib

Intervention Type: DRUG

Lazertinib will be administered orally.

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered as an intravenous (IV) infusion.

Phase 1b (expansion) Cohort E: Lazertinib and Amivantamab

Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter. Cohort E will seek to validate the immunohistochemical (IHC)-based biomarker strategy, by characterizing the activity of Amivantamab and Lazertinib combination in biomarker-positive participants with osimertinib-relapsed, but chemotherapy-naïve, EGFR Exon19del or L858R mutated NSCLC. In addition, Cohort E will seek to collect prospective data to confirm that prophylactic anticoagulation safely and effectively decreases the incidence of VTE events for patients treated with the combination of Amivantamab and Lazertinib, using Cohort F as reference.

Group Type: EXPERIMENTAL

Lazertinib

Intervention Type: DRUG

Lazertinib will be administered orally.

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered as an intravenous (IV) infusion.

Phase 1b (expansion) Cohort F: Amivantamab Monotherapy

Participants will receive Amivantamab monotherapy once weekly (QW) for 4 weeks, then every 2 weeks thereafter. Cohort F will seek to validate the IHC-based biomarker strategy, previously identified in Cohort D, by characterizing the activity of JNJ-61186372 monotherapy (Cohort F) in biomarker-positive participants with osimertinib-relapsed, but chemotherapy-naïve, EGFR Exon19del or L858R mutated NSCLC.

Group Type: EXPERIMENTAL

Amivantamab

Intervention Type: DRUG

Amivantamab will be administered as an intravenous (IV) infusion.

Interventions

Lazertinib

Lazertinib will be administered orally.

Intervention Type: DRUG

Amivantamab

Amivantamab will be administered as an intravenous (IV) infusion.

Intervention Type: DRUG

Carboplatin

Carboplatin will be administered as IV infusion.

Intervention Type: DRUG

Pemetrexed

Pemetrexed will be administered as IV infusion.

Intervention Type: DRUG

Other Intervention Names

JNJ-73841937; JNJ-61186372

Eligibility Criteria

Inclusion Criteria

• Phase 1 and Phase 1b lazertinib+Amivantamab combination cohorts: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with previously epidermal growth factor receptor (EGFR) mutation (identified locally in a Clinical Laboratory Improvement Amendments [CLIA]-certified laboratory [or equivalent]) that is metastatic or unresectable, and have progressed after standard of care front-line therapy, and exhausted available options with targeted therapy. A participant who has refused all other currently available therapeutic options is allowed to enroll
• For the Phase 1b Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP) combination cohort: histologically or cytologically confirmed advanced or metastatic EGFR-mutated NSCLC who have progressed on or after an EGFR-TKI as the most recent line of treatment with a maximum of 3 prior lines of therapy in the metastatic setting allowed
• For all expansion cohorts, the EGFR mutation must have been previously histologically or cytologically characterized, as performed by a CLIA-certified (US sites) or an accredited (outside of US) local laboratory, with a copy of the mutation analysis being submitted during screening (Phase 1b expansion Cohort B, C, D, E, and F)

1. Expansion Cohort A: Participant must have advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) that has progressed on prior treatment with osimertinib in the first or second line, followed by progression on a platinum-based chemotherapy regimen as the last line of therapy prior to study enrollment. Prior use of first or second generation EGFR tyrosine kinase inhibitor (TKI) is allowed if administered prior to osimertinib

2. Expansion Cohort B: Participant must have previously treated, advanced or metastatic NSCLC with documented primary EGFR Exon 20ins activating mutation. Participants should have been treated with standard of care, platinum-based chemotherapy regimens, but may have treated with approved EGFR TKI, investigational EGFR, or immunotherapy agents if refusing front line platinum-based chemotherapy standard of care. Up to 3 lines of prior systemic anti-cancer treatment are allowed

3. Expansion Cohort C: Participant must have advanced or metastatic NSCLC characterized by an uncommon activating mutation Additional uncommon EGFR mutations/alterations, beyond those listed above, may be considered for enrollment after agreement with the medical monitor. Participants may be treatment naïve or have been treated with one prior line of therapy which must be a first or second generation TKI (that is gefitinib, erlotinib, afatinib) in the most recent line of therapy. Prior chemotherapy is allowed if administered prior to EGFR TKI therapy, or as the only systemic anti-cancer therapy prior to study enrollment. Up to 2 lines of prior systemic anti-cancer treatment are allowed

4. Expansion Cohort D, E, and F: Participant must have advanced or metastatic EGFR-mutated NSCLC (EGFR Exon19 deletion or L858R) that has progressed on prior treatment with osimertinib in the first or second line (after first- or second-generation EGFR TKI), as the immediate prior line of therapy. Only previous treatment in the metastatic setting with a first, second, or third generation EGFR TKI is allowed. In addition, participants considered for Cohorts E and F must be eligible for, and agree to comply with, the use of prophylactic anticoagulation with a direct oral anticoagulant or a low molecular weight heparin during the first 4 months (from Day 1 through Day 120) according to national comprehensive cancer network (NCCN) or local guidelines, if assigned to the combination Cohort E

• Evaluable disease
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
• Participants must meet the study protocol defined laboratory criteria without having a history of red blood cell transfusion, platelet transfusion, or granulocyte-colony stimulating factor support within 7 days prior to the date of the test
• A woman of childbearing potential: Must have a negative serum beta human chorionic gonadotropin at screening; Must agree not to breast-feed during the study and for 6 months after the last dose of study intervention. (Enrollment is not allowed even if a woman who is breast-feeding stops breast-feeding); Must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study intervention

Exclusion Criteria

• Participant has an uncontrolled illness, including but not limited to uncontrolled diabetes, ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to study treatment] or diagnosed or suspected viral infection); active bleeding diathesis; Impaired oxygenation requiring continuous oxygen supplementation; Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of study treatment; or psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements. Any ophthalmologic condition that is either clinically unstable or requires treatment
• Prior treatment with anti programmed cell death-1 (PD-1) or anti programmed cell death-ligand 1 (PD-L1) antibody within 6 weeks of planned first dose of study intervention
• Untreated brain or other central nervous system (CNS) metastases whether symptomatic or asymptomatic. Participants who have completed definitive therapy, are not on steroids, and have a stable clinical status for at least 2 weeks prior to study treatment may be eligible for Phase 1b expansion cohorts. If brain metastases are diagnosed on Screening imaging, the participant may be enrolled, or rescreened for eligibility, after definitive treatment if above criteria are met
• Any Toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade <=2 peripheral neuropathy, and Grade <=2 hypothyroidism stable on hormone replacement therapy)
• Allergies, hypersensitivity, or intolerance to Lazertinib or JNJ-61186372 or their excipients. For the LACP combination cohort: participant has a contraindication for the use of carboplatin or pemetrexed (refer to local prescribing information for each agent). Participant has a history of hypersensitivity to, or cannot take, vitamin B12 or folic acid

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

University of California Irvine

Orange, California, United States

UCSF Helen Diller Comprehensive

San Francisco, California, United States

Stanford University Medical Center

Stanford, California, United States

Cedars Sinai Medical Center

West Hollywood, California, United States

H. Lee Moffitt Cancer & Research Institute

Tampa, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Boston University Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Washington University School Of Medicine

St Louis, Missouri, United States

Langone Health at NYC University, NYU School of Medicine

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Providence Portland Medical Center

Portland, Oregon, United States

University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

University of Washington

Seattle, Washington, United States

Beijing Cancer Hospital

Beijing, , China

The First Bethune Hospital of Jilin University

Changchun, , China

Hunan Cancer hospital

Changsha, , China

West China School of Medicine/West China Hospital, Sichuan University

Chengdu, , China

Chongqing University Cancer Hospital

Chongqing, , China

The Fifth Affiliated Hospital of Guangzhou Medical University

Guangzhou, , China

Zhejiang Cancer Hospital

Hangzhou, , China

Central Hospital of Jinan

Jinan, , China

The Second Affiliated Hospital of Kunming Medical University

Kunming, , China

Shanghai Chest Hospital

Shanghai, , China

Shengjing Hospital Of China Medical University

Shenyang, , China

Tianjin Medical University Cancer Institute and Hospital

Tianjin, , China

Union Hospital Tongji Medical College of Huazhong University of Science and Technology

Wuhan, , China

The First Affiliated Hospital of Xian Jiaotong University

Xi'an, , China

Institut Bergonie

Bordeaux, , France

Centre Leon Berard

Lyon, , France

CHU de la Timone

Marseille, , France

Institut Curie

Paris, , France

CHU De Poitiers

Poitiers, , France

HIA Begin

Saint-Mandé, , France

Institut Gustave Roussy

Villejuif, , France

Evangelische Lungenklinik Berlin

Berlin, , Germany

Uniklinik Köln

Cologne, , Germany

Kliniiken der Stadt Köln gGmbH, Krankenhaus Köln-Mehrheim

Cologne, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Klinikum der Johann Wolfgang Goethe-Universität

Frankfurt am Main, , Germany

Asklepios Klinik Gauting GmbH - Asklepios Fachkliniken Munchen-Gauting

Gauting, , Germany

Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH

Halle, , Germany

Lungenklinik Hemer

Hemer, , Germany

Pius-Hospital Oldenburg

Oldenburg, , Germany

Robert-Bosch-Krankenhaus - Klinik Schillerhoehe

Stuttgart, , Germany

IRCCS Ospedale San Raffaele

Milan, , Italy

IRCCS Istituto Europeo di Oncologia

Milan, , Italy

San Gerardo Hospital

Monza, , Italy

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, , Italy

Ospedale S. Maria Delle Croci

Ravenna, , Italy

National Cancer Center Hospital

Chūōku, , Japan

Kansai Medical University Hospital

Hirakata, , Japan

National Cancer Center Hospital East

Kashiwa, , Japan

Kobe City Medical Center General Hospital

Kobe, , Japan

Aichi Cancer Center Hospital

Nagoya, , Japan

Okayama University Hospital

Okayama, , Japan

Shizuoka Cancer Center

Shizuoka, , Japan

Oncologic Hospital, Puerto Rico Medical Center

Rio Piedras, , Puerto Rico

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hosp. Univ. Quiron Dexeus

Barcelona, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp. Gral. Univ. Gregorio Maranon

Madrid, , Spain

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Hosp Univ Fund Jimenez Diaz

Madrid, , Spain

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Hosp Univ Hm Sanchinarro

Madrid, , Spain

Hosp. Virgen Del Rocio

Seville, , Spain

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, , Taiwan

Chung Shan Medical University Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Countries

United States; China; France; Germany; Italy; Japan; Puerto Rico; South Korea; Spain; Taiwan

Other Identifiers

73841937NSC1001

Identifier Type: OTHER

Identifier Source: secondary_id

2020-000747-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506577-35-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR108656

Identifier Type: -

Identifier Source: org_study_id