Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer

NCT ID: NCT02609776

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 751 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-24
• Study Completion Date: 2026-12-31

Brief Summary

The purpose of study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of Amivantamab as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D) (monotherapy), recommended Phase 2 combination dose (RP2CD) (combination therapy), and to determine recommended Phase 2 Dose (RP2q3W) with combination chemotherapy (Amivantamab in combination with standard of care carboplatin and pemetrexed) in 21 day treatment cycle for participants with advanced non-small cell lung cancer (NSCLC).

Detailed Description

This open label (all participants know the identity of the study drug), multicenter (more than one study site), first-in-human study consists of 2 parts. Part 1 is a Amivantamab Monotherapy and Combination Dose Escalations and Part 2 Amivantamab Monotherapy and Combination Dose Expansions. In Part 1, participants with evaluable NSCLC will be enrolled into cohorts at increasing dose levels of Amivantamab monotherapy, the RP2CD of the Amivantamab and lazertinib combination which will be administered in 28 day treatment cycles, and RP2q3W of Amivantamab in combination with standard of care carboplatin and pemetrexed (chemotherapy combination) which will be administered in 21 day treatment cycles. The dose will be escalated until the maximum tolerated dose (MTD, or maximum administered dose [MAD], if no MTD is found) is reached. Part 1 will follow a traditional 3+3 design. At each dose level, 3 participants will complete Cycle 1. If no dose limiting toxicity (DLT) occurs in these 3 participants, then escalation will continue in a new cohort of 3 participants. Data from Part 1 will be used to determine one or more RP2D regimen(s). In Part 2, participants with documented epidermal growth factor receptor (EGFR) mutations and measurable disease, whose disease has progressed after previous treatment will be enrolled and receive Amivantamab at the RP2D determined in Part 1 as a monotherapy at the RP2D regimen(s), or in combination with lazertinib at the RP2CD regimen. For both parts, the study consists of following periods: an optional pre-Screening period; a Screening period (up to 28 days prior to the first dose of study drug); a Treatment period (first dose of study drug until 30(+7) days after the last dose of study drug or prior to starting any subsequent anti-cancer treatment, whichever comes first); and a Follow Up period (approximately 6 months). All participants will be followed for survival in the post-treatment follow-up period until the end of study and safety will be monitored throughout the study.

Conditions

Non-Small-Cell Lung Cancer

Keywords

Non-Small-Cell Lung Cancer; Amivantamab; First-in-Human; Human Bispecific Epidermal Growth Factor Receptor (EGFR); c-Mesenchymal-Epithelial Transition (cMet) Antibody; JNJ372; Exon 20; Exon 20 insertion; Tyrosine Kinase Inhibitor (TKI) Resistant; TKI Resistance; EGFR C797s; Met Amplification; Met + EGFR bispecific

Study Design

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

Study Groups

Part 1:Amivantamab Monotherapy+Combination Dose Escalations

The first cohort of participants will receive intravenous (IV) infusions of Amivantamab 140 milligram (mg) as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level. Dose escalation will continue until maximum tolerated dose is reached or all planned doses are administered. Participants will receive IV infusion of Amivantamab once weekly during cycle 1 and once every 2 weeks during subsequent cycles (duration of each treatment cycle is 28 days). Participants will receive lazertinib and Amivantamab on Cycle 1 Day 1 (C1D1) prior to initiation of Amivantamab (C1D1) at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily thereafter, on 28-day Amivantamab treatment cycle. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with standard of care carboplatin and pemetrexed.

Group Type: EXPERIMENTAL

Amivantamab

Intervention Type: DRUG

The first cohort of participants will receive IV infusions of Amivantamab 140 mg as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level until maximum tolerated dose is reached or all planned doses are administered. Participants will receive lazertinib and Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. The duration of each treatment cycle is 28 days. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with the administration of standard of care carboplatin and pemetrexed.

Lazertinib

Intervention Type: DRUG

Lazertinib will be administered in combination with Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily on the 28-day Amivantamab treatment cycle.

Carboplatin

Intervention Type: DRUG

Participants will receive carboplatin in combination with pemetrexed and Amivantamab as an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.

Pemetrexed

Intervention Type: DRUG

Participants will receive pemetrexed in combination with carboplatin and Amivantamab as an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.

Part 2:Amivantamab Monotherapy+Combination Dose Expansion

Participants will receive IV infusion of Amivantamab as monotherapy at Phase 2 dose (RP2D) regimen or in combination lazertinib at the recommended Phase 2 combination dose (RP2CD) regimen as determined in Part 1. The purpose of dose expansion is to further evaluate safety, tolerability, pharmacokinetic, and to assess preliminary efficacy in monotherapy and combination therapy cohorts.

Group Type: EXPERIMENTAL

Amivantamab

Intervention Type: DRUG

Participants will receive IV infusion of Amivantamab as monotherapy at RP2D regimen or in combination lazertinib at RP2CD regimen as determined in Part 1.

Lazertinib

Intervention Type: DRUG

Lazertinib will be administered in combination with Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily on the 28-day Amivantamab treatment cycle.

Interventions

Amivantamab

The first cohort of participants will receive IV infusions of Amivantamab 140 mg as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level until maximum tolerated dose is reached or all planned doses are administered. Participants will receive lazertinib and Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. The duration of each treatment cycle is 28 days. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with the administration of standard of care carboplatin and pemetrexed.

Intervention Type: DRUG

Amivantamab

Participants will receive IV infusion of Amivantamab as monotherapy at RP2D regimen or in combination lazertinib at RP2CD regimen as determined in Part 1.

Intervention Type: DRUG

Lazertinib

Lazertinib will be administered in combination with Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily on the 28-day Amivantamab treatment cycle.

Intervention Type: DRUG

Carboplatin

Participants will receive carboplatin in combination with pemetrexed and Amivantamab as an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.

Intervention Type: DRUG

Pemetrexed

Participants will receive pemetrexed in combination with carboplatin and Amivantamab as an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.

Intervention Type: DRUG

Other Intervention Names

JNJ-61186372; JNJ-61186372; JNJ-73841937; YH25448

Eligibility Criteria

Inclusion Criteria

• Participant must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) that is metastatic or unresectable. Participants must have either progressed after prior standard of care therapy (Cohorts C and hepatocyte growth factor receptor gene [MET]-1: epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKI]; Cohort D: platinum-based chemotherapy; MET-2: per regional standard of care; Cohorts wild-type adenocarcinoma (WT-Ad) and wild-type squamous cell carcinoma (WT-Sq): platinum-containing chemotherapy and programmed death- 1/ ligand-1 (PD-1/L1) therapy, either as a combined regimen or as separate lines of therapy) for metastatic disease, or be ineligible for, or have refused all other currently available therapeutic options. In cases where participants refuse currently available therapeutic options, this must be documented in the study records. For Part 1 Chemotherapy Combination Cohort only: Participants must have histologically or cytologically confirmed NSCLC that is metastatic or unresectable and be eligible for treatment with combination carboplatin and pemetrexed, in accordance with standard of care, and be willing to receive additional investigational therapy with Amivantamab
• For Part 1 Combination Dose Escalation with lazertinib only: Participants must have been diagnosed with EGFR Exon 19del or L858R activating mutation and (a) be treatment naïve for metastatic disease, without access to third generation TKI in the front-line setting, or (b) have progressed after front-line treatment with first (erlotinib or gefitinib) or second generation (afatinib) TKI and are ineligible for Cohort MET-1, or (c) have been treated with a third generation TKI (e.g., osimertinib) in either the front line or second-line setting, and are not eligible for enrollment in either Cohort C or MET-1. For Part 1 Chemotherapy Combination Cohort: Participants may be diagnosed with EGFR mutated or EGFR wild type NSCLC. For Part 2 Cohorts C, D, MET-1, and MET-2 only: Participants must also have disease with a previously diagnosed activating epidermal growth factor receptor (EGFR) mutation (includes both inhibitor sensitive primary mutations such as Exon 19 deletion and L858R (Cohort C, E, and MET-1), as well as marketed TKI-resistant mutations such as Exon 20 insertion (Cohort C, D and MET-1) or activating cMet Exon 14 skipping mutation (Cohort MET-2). Documentation of primary activating EGFR or cMet mutation eligibility by CLIA-certified laboratory (or equivalent) testing is required. For Part 2 Cohorts WT-Ad and WT-Sq: Participants must have wild-type EGFR, anaplastic lymphoma kinase (ALK), and absence of MET Exon 14 skipping mutation as tested by the Food and Drug Administration (FDA) approved test or a CLIA-certified laboratory (or equivalent). The pathology report or equivalent must be in the medical record for verification. Where testing for EGFR and ALK are not part of standard of care for participants with squamous cell carcinoma histology, documentation of the absence of these mutations is not necessary for enrollment into the WT-Sq cohort
• For Part 1: Participant must have evaluable disease. For Part 2: Participant must have measurable disease according to Response Criteria in Solid Tumors (RECIST) v1.1
• For Part 2: Cohorts A and B: Participants EGFR mutated disease must have most recently progressed following treatment with a marketed EGFR inhibitor. Exception: In participants diagnosed with mutations associated with de novo EGFR inhibitor resistance (for example, Exon 20 insertions), only previous treatment with combination platinum-based chemotherapy is required. Cohort C: Participants with primary EGFR mutated disease, with a documented EGFR alteration (example, C797S) mediating resistance to previous treatment with a third generation EGFR TKI (for example, osimertinib), in participants with primary Exon 20ins disease, the documented EGFR alteration may arise following treatment with a TKI with known activity against Exon 20ins disease (for example, poziotinib). Cohort D: participants must have been previously diagnosed with an EGFR Exon 20 insertion and have not been previously treated with a TKI with known activity against Exon 20ins disease (example, poziotinib). Cohort MET-1: Participants with documented primary EGFR mutated disease and documented MET amplification or MET mutation after progression on any EGFR TKI. Participants with disease characterized by both MET amplification and EGFR resistance mutations to prior third generation EGFR TKI will be preferentially enrolled into Cohort C. Participants may have received or have been intolerant to prior platinum-based chemotherapy. Cohort MET-2: Participants with documented primary MET Exon 14 skipping mutation non-small cell lung cancer (NSCLC). Cohort E (combination Amivantamab and lazertinib): Participants must have been diagnosed with EGFR Exon 19del or L858R activating mutation and have progressed after first or second-line treatment with a third generation TKI (e.g., osimertinib). Cohort WT-Ad: Participant must have been diagnosed with NSCLC of adenocarcinoma histology, with positive EGFR and/or MET expression as detected on a validated immunohistochemistry (IHC) assay performed by the central laboratory and have progressed on prior platinum containing chemotherapy and PD-1/L1 therapy, either as a combined regimen or as a separate line of therapy. Eligibility may be determined through IHC analysis of either archival (pre-screening) or mandatory fresh tumor tissue collected during the Screening period. Cohort WT-Sq: Participant must have been diagnosed with NSCLC of squamous cell carcinoma histology, with positive EGFR and/or MET expression as detected on a validated IHC assay performed by the central laboratory and have progressed on prior platinum-containing chemotherapy and PD-1/L1 therapy, either as a combined regimen or as a separate line of therapy. Eligibility may be determined through IHC analysis of either archival (pre-screening) or mandatory fresh tumor tissue collected during the Screening
• Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria

• Participant has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension, or diabetes, ongoing or active infection, (that is, has discontinued all antibiotics for at least one week prior to first dose of study drug), or psychiatric illness/social situation that would limit compliance with study requirements. Participants with medical conditions requiring chronic continuous oxygen therapy are excluded. For Part 1 Chemotherapy Combination Cohort only: additionally, participants with active bleeding diathesis
• Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives whichever is longer, before the first administration of study drug. For agents with long half-lives, the maximum required time since last dose is 4 weeks. Toxicities from previous anti-cancer therapies should have resolved to baseline levels or to Grade 1 or less, (except for alopecia [any grade], Grade less than or equal to [<=] 2 peripheral neuropathy, and Grade less than [<] 2 hypothyroidism stable on hormone replacement). For Part 1 Combination Dose Escalation: Any previous treatment with systemic anti-cancer immunotherapy, including but not limited to anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents. For Part 1 Chemotherapy Combination Cohort only: Any previous treatment with systemic anti-cancer immunotherapy in the past 3 months or localized radiotherapy to lung within the past 6 months. For Part 2 only: Cohorts A and B: Prior treatment with chemotherapy for metastatic disease is not allowed unless the tumor mutation carries de-novo resistance to EGFR TKI (example, Exon 20 insertions). Cohort C and MET-1: Prior treatment with more than 2 lines of cytotoxic chemotherapy for metastatic disease (maintenance therapy is not included). Cohort D: Previous treatment with an EGFR TKI with activity against EGFR Exon 20 insertions (such as poziotinib). Cohort E (combination Amivantamab and lazertinib): Any previous treatment in the metastatic setting with other than a first, second, or third generation EGFR TKI. Cohorts WT-Ad and WT-Sq: more than three lines of prior systemic therapy in the metastatic setting
• Participants with untreated brain metastases. Participants with definitively, locally-treated metastases that are clinically stable and asymptomatic for at least 2 weeks and who are off or receiving low-dose corticosteroid treatment (<=10 mg prednisone or equivalent) for at least 2 weeks prior to study treatment are eligible. Exception: participants with asymptomatic, untreated brain metastases, each less than 1 cm in diameter, may be eligible for Amivantamab and lazertinib combination therapy in the Part 1 Combination Dose Escalation or Part 2 Combination Expansion Cohort E
• Participant has a history of malignancy other than the disease under study within 3 years before Screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with or minimal risk of recurrence within a year from Screening)
• Participant has not fully recovered from major surgery or significant traumatic injury prior the first dose of study drug or expects to have major surgery during the study period or within 6 months after the last dose of study drug
• Participant has, or will have, any of the following: a. An invasive operative procedure with entry into a body cavity, within 4 weeks or without complete recovery before Cycle 1 Day 1. Thoracentesis, if needed, and percutaneous biopsy for baseline tumor tissue sample may be done less than 4 weeks prior to Cycle 1 Day 1, as long as the participant has adequately recovered from the procedure prior to the first dose of study drug in the clinical judgement of the investigator; b. Significant traumatic injury within 3 weeks before the start of Cycle 1 Day 1 (all wounds must be fully healed prior to Day 1); c. Any medical condition that requires intact wound healing capacity and is expected to endanger subject safety if wound healing capacity would be severely reduced during administration of the investigational agent; d. Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study drug

• 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

Duarte, California, United States

La Jolla, California, United States

Orange, California, United States

Santa Monica, California, United States

West Hollywood, California, United States

Tampa, Florida, United States

Chicago, Illinois, United States

Bethesda, Maryland, United States

Boston, Massachusetts, United States

Detroit, Michigan, United States

Rochester, Minnesota, United States

St Louis, Missouri, United States

New York, New York, United States

Portland, Oregon, United States

Philadelphia, Pennsylvania, United States

Houston, Texas, United States

Fairfax, Virginia, United States

Camperdown, , Australia

Heidelberg, , Australia

Kogarah, , Australia

Murdoch, , Australia

Woolloongabba, , Australia

Toronto, Ontario, Canada

Beijing, , China

Changchun, , China

Changsha, , China

Chengdu, , China

Chongqing, , China

Guangzhou, , China

Hangzhou, , China

Hefei, , China

Nanchang, , China

Nanjing, , China

Wuhan, , China

Zhengzhou, , China

Bordeaux, , France

Dijon, , France

Lyon, , France

Marseille, , France

Paris, , France

Saint-Herblain, , France

Villejuif, , France

Chūōku, , Japan

Hyōgo, , Japan

Kashiwa, , Japan

Kurume, , Japan

Nagoya, , Japan

Niigata, , Japan

Osaka, , Japan

Tokyo, , Japan

Wakayama, , Japan

Yonago, , Japan

Cheongju-si, , South Korea

Goyang-si, , South Korea

Incheon, , South Korea

Seongnam-si, , South Korea

Seoul, , South Korea

A Coruña, , Spain

Barcelona, , Spain

Madrid, , Spain

Málaga, , Spain

Santander, , Spain

Seville, , Spain

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Taipei, , Taiwan

Manchester, , United Kingdom

Newcastle upon Tyne, , United Kingdom

Sutton, , United Kingdom

Countries

Italy; United States; Australia; Canada; China; France; Japan; South Korea; Spain; Taiwan; United Kingdom

References

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Other Identifiers

61186372EDI1001

Identifier Type: OTHER

Identifier Source: secondary_id

2018-003908-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108064

Identifier Type: -

Identifier Source: org_study_id