A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer
Condition(s) studied
Investigational drug(s) / intervention(s)
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.
Study 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).
Eligibility
Primary outcome measure(s)
- Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1) — Until the end of first cycle (21 days for Phase 1)
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher. - Percentage of Participants with Dose-Limiting Toxicity (DLT) (Phase 1b) — Until the end of first cycle (28 days for Phase 1b)
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher. - Overall Response Rate (ORR) (Phase 1b Expansion Cohorts A-D) — Up to 2.5 years
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. - Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability (Phase 1b Expansion Cohorts A-E) — Up to 2.5 years
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. - Percentage of Participants with DLT (Phase 1b combination Lazertinib, Amivantamab, Platinum-doublet chemotherapy [LACP]) — Until the end of first cycle (21 days for Phase 1b combination LACP)
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher. - Number of Participants with AEs as a Measure of Safety and Tolerability (Phase 1b combination LACP) — Up to 2.5 years
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. - 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) — Up to 2.5 years
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). - ORR Among Participants with MET3+ Staining on Greater Than or Equal to (>=)25 Percent (%) of Tumor Cells (Phase 1b Expansion Cohorts E and F) — Up to 2.5 years
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. - Duration of Response (DOR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F) — Up to 2.5 years
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. - Clinical Benefit Rate (CBR) Among Participants with MET3+ Staining on >=25% of Tumor Cells (Phase 1b Expansion Cohorts E and F) — Up to 2.5 years
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.
Trial sites (78)
| Facility | City | Region | Status |
|---|---|---|---|
| USC Norris Comprehensive Cancer Center | Los Angeles | California | |
| University of California Irvine | Orange | California | |
| UCSF Helen Diller Comprehensive | San Francisco | California | |
| Stanford University Medical Center | Stanford | California | |
| Cedars Sinai Medical Center | West Hollywood | California | |
| H. Lee Moffitt Cancer & Research Institute | Tampa | Florida | |
| Massachusetts General Hospital | Boston | Massachusetts | |
| Dana Farber Cancer Institute | Boston | Massachusetts | |
| Boston University Medical Center | Boston | Massachusetts | |
| Barbara Ann Karmanos Cancer Institute | Detroit | Michigan | |
| Washington University School Of Medicine | St Louis | Missouri | |
| Langone Health at NYC University, NYU School of Medicine | New York | New York | |
| Columbia University Medical Center | New York | New York | |
| Providence Portland Medical Center | Portland | Oregon | |
| University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine | Philadelphia | Pennsylvania | |
| Huntsman Cancer Institute | Salt Lake City | Utah | |
| Virginia Cancer Specialists | Fairfax | Virginia | |
| University of Washington | Seattle | Washington | |
| 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 |
+ 38 more sites — see the full list on the official registry below.
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT04077463 on ClinicalTrials.gov ↗ ← All trials in Italy