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

Carcinoma, Non-Small-Cell Lung Clinical Trial

— Chrysalis-2  

Official title:

An Open-label Phase 1/1b Study to Evaluate the Safety and Pharmacokinetics of JNJ-73841937 (Lazertinib), a Third Generation EGFR-TKI, as Monotherapy or in Combinations With JNJ-61186372, a Human Bispecific EGFR and cMet Antibody in Participants With Advanced Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04077463
• Other study ID #: CR108656
• Secondary ID: 73841937NSC10012
• Status: Recruiting
• Phase: Phase 1
• Start date: September 4, 2019
• Est. completion date: February 14, 2027

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 460
• Est. completion date: February 14, 2027
• Est. primary completion date: February 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Lazertinib
Lazertinib will be administered orally.
• Amivantamab
Amivantamab will be administered as an intravenous (IV) infusion.
• Carboplatin
Carboplatin will be administered as IV infusion.
• Pemetrexed
Pemetrexed will be administered as IV infusion.

Locations

Country	Name	City	State
China	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	Hang Zhou
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	Xian
France	Institut Bergonie	Bordeaux
France	Centre Leon Berard	Lyon Cedex 8
France	CHU de la Timone	Marseille
France	Institut Curie	Paris
France	CHU De Poitiers	Poitiers
France	HIA Begin	Saint Mande
France	Institut Gustave Roussy	Villejuif Cedex
Germany	Evangelische Lungenklinik Berlin	Berlin
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 (Saale)
Germany	Lungenklinik Hemer	Hemer
Germany	Kliniiken der Stadt Köln gGmbH, Krankenhaus Köln-Mehrheim	Köln
Germany	Uniklinik Köln	Köln
Germany	Pius-Hospital Oldenburg	Oldenburg
Germany	Robert-Bosch-Krankenhaus - Klinik Schillerhoehe	Stuttgart
Italy	IRCCS Istituto Europeo di Oncologia	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	San Gerardo Hospital	Monza
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Ospedale S. Maria Delle Croci	Ravenna
Japan	National Cancer Center Hospital	Chuo Ku
Japan	Kansai Medical University Hospital	Hirakata
Japan	National Cancer Center Hospital East	Kashiwa
Japan	Kobe City Medical Center General Hospital	Kobe City
Japan	Aichi Cancer Center Hospital	Nagoya Shi
Japan	Okayama University Hospital	Okayama
Japan	Shizuoka Cancer Center	Shizuoka
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Puerto Rico	Oncologic Hospital, Puerto Rico Medical Center	Rio Piedras
Spain	Hosp. Univ. Quiron Dexeus	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp Univ Fund Jimenez Diaz	Madrid
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. Hm Sanchinarro	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hosp. Virgen Del Rocio	Seville
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei City
United States	Boston University Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	USC - Norris Comprehensive Cancer Center	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	Langone Health at NYC University, NYU School of Medicine	New York	New York
United States	University of California Irvine	Orange	California
United States	University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCSF Helen Diller Comprehensive	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California
United States	H. Lee Moffitt Cancer & Research Institute	Tampa	Florida
United States	Cedars Sinai Medical Center	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  China,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Puerto Rico,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1)	DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.	Until the end of first cycle (21 days for Phase 1)
Primary	Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1b)	DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.	Until the end of first cycle (28 days for Phase 1b)
Primary	Overall Response Rate (ORR) (Phase 1b Expansion Cohorts A-D)	ORR is defined as the percentage of participants who achieve either a complete (CR) or partial response (PR) as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Primary	Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1b Expansion Cohorts A-E)	Adverse events (AEs) defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Criteria Version 5.0 in participants treated at the RP2CD regimen of Lazertinib and Amivantamab combination therapy. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 2.5 years
Primary	Percentage of Participants with DLT (Phase 1b combination Lazertinib, Amivantamab, Platinum-doublet chemotherapy [LACP])	DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.	Until the end of first cycle (21 days for Phase 1b combination LACP)
Primary	Number of Participants with AEs as a Measure of Safety and Tolerability (Phase 1b combination LACP)	AEs defined by the NCI-CTCAE criteria version 5.0 in participants treated with LACP combination regimen. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 2.5 years
Primary	Overall Response Rate (ORR) per RECIST version 1.1 (v1.1) with NGS Analysis of Circulating Tumor ctDNA, IHC Analysis of EGFR and MET Expression (Phase 1b Expansion Cohort D)	ORR is defined as the percentage of participants who achieve either a complete (CR) or partial response (PR) as determined by the investigator using RECIST 1.1 criteria with Next Generation Sequencing (NGS) Analysis of Circulating Tumor Deoxyribonucleic Acid (ctDNA), Immunohistochemical (IHC) Analysis of Tumor Epidermal Growth Factor Receptor (EGFR) and MET Expression (Phase 1b Expansion Cohort D).	Up to 2.5 years
Primary	ORR Among Participants with MET3+ Staining on Greater Than or Equal to (>=)25 Percent (%) of Tumor Cells (Phase 1b Expansion Cohorts E and F)	ORR among participants with MET3+ staining on >=25 % of tumor cells will be reported. ORR is defined as the percentage of participants who achieve either a CR or PR as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Primary	Duration of Response (DOR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F)	DOR among participants with MET3+ staining on >=25 % of tumor cells will be reported. DOR will be calculated as time from initial response of CR or PR to progressive disease (PD) or death due to any cause, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Primary	Clinical Benefit Rate (CBR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F)	CBR among participants with MET3+ staining on >=25% of tumor cells will be reported. CBR is defined as the percentage of participants achieving complete or partial response, or durable stable disease (duration of at least 11 weeks) as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Secondary	Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1 and Phase 1b)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 2.5 years
Secondary	Plasma Concentration of Lazertinib (Phase 1 and Phase 1b)	Plasma samples will be analyzed to determine concentrations of Lazertinib.	Up to End of Treatment [EOT]) (30 days after last dose) (up to 2.5 years)
Secondary	Serum Concentration of Amivantamab (Phase 1b)	Serum samples will be analyzed to determine concentrations of Amivantamab.	Up to EOT (30 days after last dose) (up to 2.5 years)
Secondary	Number of Participants with Anti-drug Antibodies Against Amivantamab (Phase 1b)	Number of participants with anti-drug antibodies against Amivantamab will be reported.	Up to EOT (30 days after last dose) (up to 2.5 years)
Secondary	Progression free survival (PFS) (Phase 1b Expansion)	PFS is defined as the time from first infusion of study intervention to PD or death due to any cause.	Up to 2.5 years
Secondary	Time to Treatment Failure (TTF) (Phase 1b Expansion)	TTF is defined as the time from the first administration of the study intervention to discontinuation of treatment for any reason, including disease progression, treatment toxicity, death, and will be utilized to capture clinical benefit for patients continuing treatment beyond as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Secondary	Overall Survival (OS) (Phase 1b Expansion)	OS is defined as the time from first infusion of study intervention to death due to any cause as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Secondary	Duration of Response (DOR) (Phase 1b expansion)	DOR will be calculated as time from initial response of CR or PR to progressive disease (PD) or death due to any cause, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Secondary	Clinical Benefit Rate (CBR) (Phase 1b expansion)	CBR is defined as the percentage of participants achieving complete or partial response, or durable stable disease (duration of at least 11 weeks) as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Secondary	Number of Participants with Venous Thromboembolic (VTE) Events by Severity	Number of participants with VTE events including pulmonary embolism and deep vein thrombosis by severity defined by the NCI-CTCAE Criteria Version 5.0 will be reported.	Up to 2.5 years
Secondary	Number of Participants with Adverse Events (AEs) (Phase 1b Expansion Cohort F)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 2.5 years
Secondary	ORR (Phase 1b expansion Cohorts E and F)	ORR is defined as the percentage of participants who achieve either a CR or PR as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Secondary	DOR (Phase 1b Expansion Cohorts E and F)	DOR will be calculated as time from initial response of CR or PR to PD or death due to any cause, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Secondary	CBR (Phase 1b expansion Cohorts E and F)	CBR is defined as the percentage of participants achieving complete or partial response, or durable stable disease (duration of at least 11 weeks) as determined by the investigator using RECIST 1.1 criteria.	Up to 2.5 years
Secondary	Intracranial Progression free survival (PFS) (Phase 1b Expansion E and F)	Intracranial PFS is defined as the time from first infusion of study intervention until the date of objective intracranial disease progression or death, whichever comes first, based on Investigator assessment using RECIST v1.1.	Up to 2.5 years