Clinical trial NCT04077463: A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-09-04
Enrollment: 701
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1)
timeFrame: Until the end of first cycle (21 days for Phase 1)
measure: Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1b)
timeFrame: Until the end of first cycle (28 days for Phase 1b)
measure: Overall Response Rate (ORR) (Phase 1b Expansion Cohorts A-D)
timeFrame: Up to 2.5 years
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1b Expansion Cohorts A-E)
timeFrame: Up to 2.5 years
measure: Percentage of Participants with DLT (Phase 1b combination Lazertinib, Amivantamab, Platinum-doublet chemotherapy [LACP])
timeFrame: Until the end of first cycle (21 days for Phase 1b combination LACP)
measure: Number of Participants with AEs as a Measure of Safety and Tolerability (Phase 1b combination LACP)
timeFrame: Up to 2.5 years
measure: 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)
timeFrame: Up to 2.5 years
measure: ORR Among Participants with MET3+ Staining on Greater Than or Equal to (>=)25 Percent (%) of Tumor Cells (Phase 1b Expansion Cohorts E and F)
timeFrame: Up to 2.5 years
measure: Duration of Response (DOR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F)
timeFrame: Up to 2.5 years
measure: Clinical Benefit Rate (CBR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F)
timeFrame: Up to 2.5 years
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1 and Phase 1b)
timeFrame: Up to 2.5 years
measure: Plasma Concentration of Lazertinib (Phase 1 and Phase 1b)
timeFrame: Up to End of Treatment [EOT]) (30 days after last dose) (up to 2.5 years)
measure: Serum Concentration of Amivantamab (Phase 1b)
timeFrame: Up to EOT (30 days after last dose) (up to 2.5 years)
measure: Number of Participants with Anti-drug Antibodies Against Amivantamab (Phase 1b)
timeFrame: Up to EOT (30 days after last dose) (up to 2.5 years)
measure: Progression free survival (PFS) (Phase 1b Expansion)
timeFrame: Up to 2.5 years
measure: Time to Treatment Failure (TTF) (Phase 1b Expansion)
timeFrame: Up to 2.5 years
measure: Overall Survival (OS) (Phase 1b Expansion)
timeFrame: Up to 2.5 years
measure: Duration of Response (DOR) (Phase 1b expansion)
timeFrame: Up to 2.5 years
measure: Clinical Benefit Rate (CBR) (Phase 1b expansion)
timeFrame: Up to 2.5 years
measure: Number of Participants with Venous Thromboembolic (VTE) Events by Severity
timeFrame: Up to 2.5 years
measure: Number of Participants with Adverse Events (AEs) (Phase 1b Expansion Cohort F)
timeFrame: Up to 2.5 years
measure: ORR (Phase 1b expansion Cohorts E and F)
timeFrame: Up to 2.5 years
measure: DOR (Phase 1b Expansion Cohorts E and F)
timeFrame: Up to 2.5 years
measure: CBR (Phase 1b expansion Cohorts E and F)
timeFrame: Up to 2.5 years
measure: Intracranial Progression free survival (PFS) (Phase 1b Expansion E and F)
timeFrame: Up to 2.5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Comprehensive
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: West Hollywood
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer & Research Institute
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: New York
country: United States
facility: Langone Health at NYC University, NYU School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
city: Changsha
country: China
facility: Hunan Cancer hospital
city: Chengdu
country: China
facility: West China School of Medicine/West China Hospital, Sichuan University
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Guangzhou
country: China
facility: The Fifth Affiliated Hospital of Guangzhou Medical University
city: Hang Zhou
country: China
facility: Zhejiang Cancer Hospital
city: Jinan
country: China
facility: Central Hospital of Jinan
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical University
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shenyang
country: China
facility: Shengjing Hospital Of China Medical University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College of Huazhong University of Science and Technology
city: Xian
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon Cedex 8
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: CHU de la Timone
city: Paris
country: France
facility: Institut Curie
city: Poitiers
country: France
facility: CHU De Poitiers
city: Saint Mande
country: France
facility: HIA Begin
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität
city: Gauting
country: Germany
facility: Asklepios Klinik Gauting GmbH - Asklepios Fachkliniken Munchen-Gauting
city: Halle (Saale)
country: Germany
facility: Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH
city: Hemer
country: Germany
facility: Lungenklinik Hemer
city: Köln
country: Germany
facility: Uniklinik Köln
city: Köln
country: Germany
facility: Kliniiken der Stadt Köln gGmbH, Krankenhaus Köln-Mehrheim
city: Oldenburg
country: Germany
facility: Pius-Hospital Oldenburg
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus - Klinik Schillerhoehe
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: IRCCS Istituto Europeo di Oncologia
city: Monza
country: Italy
facility: San Gerardo Hospital
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
city: Ravenna
country: Italy
facility: Ospedale S. Maria Delle Croci
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Kobe City
country: Japan
facility: Kobe City Medical Center General Hospital
city: Nagoya Shi
country: Japan
facility: Aichi Cancer Center Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Rio Piedras
country: Puerto Rico
facility: Oncologic Hospital, Puerto Rico Medical Center
city: Barcelona
country: Spain
facility: Hosp. Univ. Quiron Dexeus
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp Univ Hm Sanchinarro
city: Seville
country: Spain
facility: Hosp. Virgen Del Rocio
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: