A Study of Clinical Outcomes in Participants With EGFR Mutated Advanced Non-Small Cell Lung Cancer (NSCLC) in a Real-World Setting (LEPIDOPTERA)

Prospective, Multi Country, Observational Study of Clinical Outcomes in EGFR-mutated, Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated With Approved Amivantamab-containing Regimens Under Standard Clinical Practice

The purpose of this study is to describe the clinical and health-related outcomes of amivantamab-containing regimens for the treatment of common epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC; most common type of lung cancer) in a real-world setting. Metastatic NSCLC is when this disease spreads to other parts of body. NSCLC may occur due to mutations (changes) in many genes including epidermal growth factor receptor (EGFR).

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung

• Study Type: Observational
• Enrollment (Estimated): 380

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Study Locations

• Austria
  • Graz, Austria, 8036
    • Recruiting
    • University Hospital Graz
  • Klagenfurt, Austria, 9020
    • Recruiting
    • Klinikum Klagenfurt am Wörthersee
• Belgium
  • Brussels, Belgium, 1090
    • Recruiting
    • UZ Brussel
  • Kortrijk, Belgium, 8500
    • Recruiting
    • AZ Groeninge
  • Sint-Niklaas, Belgium, 9100
    • Recruiting
    • VITAZ
• Czechia
  • Brno, Czechia, 625 00
    • Recruiting
    • Fakultni nemocnice Brno
  • Hradec Králové, Czechia, 500 05
    • Recruiting
    • Fakultni Nemocnice Hradec Kralove
  • Olomouc, Czechia, 77900
    • Recruiting
    • Fakultni nemocnice Olomouc
  • Prague, Czechia, 140 59
    • Recruiting
    • Fakultni Thomayerova nemocnice
• Germany
  • Aschaffenburg, Germany, 63739
    • Recruiting
    • MVZ am Klinikum Aschaffenburg Onkologie
  • Bielefeld, Germany, 33611
    • Recruiting
    • Evangelisches Klinikum Bethel
  • Bochum, Germany, 44791
    • Recruiting
    • Augusta Kliniken Bochum Hattingen
  • Chemnitz, Germany, 09113
    • Recruiting
    • Klinikum Chemnitz gGmbH
  • Cologne, Germany, 50677
    • Recruiting
    • Haematologie u Onkologie Koeln MV Zentrum
  • Essen, Germany, 45136
    • Recruiting
    • Kliniken Essen-Mitte; Evangelische Huyssens-Stiftung
  • Hamburg, Germany, 20249
    • Recruiting
    • Facharztzentrum Eppendorf
  • Hanover, Germany, 30161
    • Recruiting
    • Onkologie am Raschplatz
  • Hanover, Germany, 30449
    • Recruiting
    • Klinikum Region Hannover Klinikum Siloah
  • Hemer, Germany, 58675
    • Recruiting
    • Lungenklinik Hemer
  • Konstanz, Germany, 78464
    • Recruiting
    • Klinikum Konstanz
  • Neuss, Germany, 41462
    • Recruiting
    • MVZ fur Hamatologie und Onkologie Rhein Kreis GmbH
  • Recklinghausen, Germany, 45659
    • Recruiting
    • Knappschaft Kliniken MVZ Nord GmbH
  • Stolberg, Germany, 52222
    • Recruiting
    • MVZ Onkologie Groschek Keller
  • Ulm, Germany, 89081
    • Recruiting
    • Bundeswehrkrankenhaus Ulm
• Israel
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Rabin Medical Center
  • Ramat Gan, Israel, 5262000
    • Recruiting
    • Sheba Medical Center
  • Tel Aviv, Israel, 6971028
    • Recruiting
    • Assuta MC
• Italy
  • Avellino, Italy, 83100
    • Recruiting
    • Ospedale San Giuseppe Moscati di Avellino
  • Bari, Italy, 70124
    • Recruiting
    • Oncologia Medica - Irccs - Istituto Tumori Giovanni Paolo II
  • Brescia, Italy, 25123
    • Recruiting
    • ASST Spedali Civili Brescia
  • Candiolo, Italy, 10060
    • Recruiting
    • Istituto di Candiolo, IRCCS
  • Catania, Italy, 95123
    • Recruiting
    • PO G.Rodolico, AOU Policlinico-Vittorio Emanuele Catania
  • Catanzaro, Italy, 88100
    • Recruiting
    • Azienda Ospedaliera Pugliese Ciaccio Catanzaro
  • Genova, Italy, 16132
    • Recruiting
    • Ospedale Policlinico San Martino IRCCS
  • Lecce, Italy, 73100
    • Recruiting
    • Azienda Ospedaliera ''Vito Fazzi''
  • Milan, Italy, 20141
    • Recruiting
    • European Institute of Oncology
  • Milan, Italy, 20162
    • Recruiting
    • ASST Grande Ospedale Metropolitano Niguarda
  • Milan, Italy, 20132
    • Recruiting
    • San Raffaele Hospital
  • Milan, Italy, 20133
    • Recruiting
    • Istituto Dei Tumori Di Milano
  • Naples, Italy, 80131
    • Recruiting
    • Fondazione G Pascale Istituto Nazionale Tumori IRCCS
  • Novara, Italy, 28100
    • Recruiting
    • Azienda Ospedaliero Universitaria Maggiore della Carità di Novara
  • Olbia, Italy, 07026
    • Recruiting
    • ASL Gallura - Ospedale Giovanni Paolo II
  • Palermo, Italy, 90127
    • Recruiting
    • Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
  • Palermo, Italy, 90146
    • Recruiting
    • A.O.R Villa Sofia Cervello
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario A Gemelli IRCCS
  • Roma, Italy, 128
    • Recruiting
    • Campus Bio Medico di Roma
  • Sassari, Italy, 07100
    • Recruiting
    • Azienda Ospedaliero Universitaria Di Sassari
  • Torrette-Ancona, Italy, 60126
    • Recruiting
    • Ospedali Riuniti di Ancona
• Spain
  • Córdoba, Spain, 14004
    • Recruiting
    • Hosp Reina Sofia
  • Jerez de la Frontera, Spain, 11407
    • Recruiting
    • Hosp. de Jerez de La Frontera
  • Lugo, Spain, 27003
    • Recruiting
    • Hosp. Univ. Lucus Augusti
  • Ourense, Spain, 32005
    • Recruiting
    • Complexo Hosp. Univ. de Ourense
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen Rocio
  • Valladolid, Spain, 47003
    • Recruiting
    • Hosp. Clinico Univ. de Valladolid
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • Recruiting
    • Royal United Hospital
  • Eastbourne, United Kingdom, BN21 2UD
    • Recruiting
    • Eastbourne District General Hospital
  • Heath Town, United Kingdom, WV10 0QP
    • Recruiting
    • New Cross Hospital
  • London, United Kingdom, SW3 6JJ
    • Recruiting
    • Royal Marsden Hospital
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust Christie Hospital
  • Sutton, United Kingdom, SM2 5PT
    • Recruiting
    • Royal Marsden Hospital (Sutton)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will include participants with advanced NSCLC.

Description

Inclusion Criteria:

• Participant has a confirmed diagnosis of common epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) (EGFR exon 19 deletions or exon 21 L858R substitution) and is eligible for an amivantamab-containing regimen per the judgment of the treating physician and in alignment with the approved amivantamab indications and recommended prophylactic and reactive medication as described in the local specific summary of product characteristics (SmPC) for amivantamab
• Participants or their legally acceptable representative, where applicable, must sign a participation agreement/Informed consent form (ICF) allowing source data verification in accordance with local requirements
• Participant is being planned to be initiated with an amivantamab-containing regimen for the first time within 4 weeks following the visit for start of data collection
• Decision to administer an amivantamab-containing regimen has been made prior to participant's enrollment in the study and is separate from the physician's decision to include the participant in the current study

Exclusion criteria:

• At the time of the initiation of the amivantamab-containing regimen, the participant is receiving an active systemic anticancer treatment for advanced NSCLC that is not included in the locally approved combination regimen with amivantamab (regardless of whether it is part of an interventional study). One cycle of platinum-based chemotherapy (for example, carboplatin-pemetrexed) is permitted prior to the first dose of amivantamab in a 1L while awaiting biopsy results
• Participant has received prior treatment with amivantamab in a clinical trial or for compassionate use
• Participants who are not receiving amivantamab but are being treated with a biosimilar or a non-original biologic agent
• Participants with conditions listed in the contraindications of the SmPC for amivantamab or other agents essential for the applicable amivantamab-containing treatment regimen (lazertinib/ platinum/ pemetrexed)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cohort C: Amivantamab and lazertinib; Participants with confirmed diagnosis of advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations (first-line therapy) who received at least 1 dose of amivantamab in combination with lazertinib as per standard clinical practice will be enrolled. No drug will be provided as part of this study. Only data available within routine clinical practice will be collected in this study.
Cohort B: Amivantamab with carboplatin and pemetrexed; Participants with confirmed diagnosis of advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations after failure of prior therapy including an EGFR TKI, who received at least 1 dose of amivantamab in combination with carboplatin and pemetrexed, as per standard clinical practice will be enrolled. No drug will be provided as part of this study. Only data available within routine clinical practice will be collected in this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-World Time to Treatment Discontinuation (rwTTD)	rwTTD is defined as the time from the date of initiation of the amivantamab-containing regimen to discontinuation of the full amivantamab containing regimen for any reason, including disease progression, treatment toxicity or death.	Up to approximately 60 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-World Progression-Free Survival (rwPFS)	rwPFS is defined as the time from the date of initiation of the amivantamab-containing regimen to the date of investigator-determined disease progression (radiological or clinical) or death due to any cause, whichever occurs first.	Up to approximately 60 Months
Real-World Time to Next Treatment (rwTTNT)	rwTTNT is defined as the time from initiation of the amivantamab-containing regimen to start of a subsequent systemic treatment following discontinuation of the full amivantamab-containing regimen or death, whichever occurs first.	Up to approximately 60 Months
Real-World Overall Survival (rwOS)	rwOS is defined as the time from the date of initiation of the amivantamab-containing regimen to the date of death from any cause or reason.	Up to approximately 60 Months
Real-World Time to Subsequent Treatment Discontinuation (rwTTD2)	rwTTD2 is defined as the time from initiation of the amivantamab-containing regimen to the discontinuation of the first subsequent therapy for any reason, including disease progression, treatment toxicity or death.	Up to approximately 60 Months
Number of Participants with Adverse Events (AEs) by Severity	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 approximately 60 Months
Number of Participants with Dose Modifications and Discontinuations of Amivantamab, Lazertinib and Chemotherapy	Participants with Dose Modifications and Discontinuations of Amivantamab, Lazertinib and Chemotherapy will be reported.	Up to approximately 60 Months
Number of Participants Using Concomitant Medications	Participants using concomitant medications including those to manage specific AEs related to the amivantamab-containing regimen, namely infusion related reactions (IRRs), venous thromboembolism (VTEs), and dermatologic AEs including paronychia, will be reported.	Up to approximately 60 Months
Health-Related Quality of Life (HRQoL) Assessed by SKINDEX Scale Score	The SKINDEX-16 measures how a participant's skin condition impacts their health-related quality of life. There are 16 questions on a 7-point scale, ranging from 0 (never bothered) to 6 (always bothered). The questionnaire is divided into 3 domains: symptoms (items 1 to 4), emotions (items 5 to 11), and functionality (items 12 to 16). An overall score is the average of the 3 domain scores. All domain scores will be linearly transformed to be in the range from 0 to 100. A score of 0 indicates that the skin condition has no impact on QoL, while a score of 100 indicates the worst possible impact.	Up to approximately 60 Months
Quality of Life Assessed by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) Items-30 Scale Score	The EORTC QLQ-C30 is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), a global health status / quality of life scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, and more severe symptoms.	Up to approximately 60 Months
Quality of Life Impact on Questions Regarding Reactive and Prophylactic Management of AEs Related to the Amivantamab-Containing Regimen	Three questions regarding reactive and prophylactic management of AEs related to the amivantamab-containing regimen will be reported. These questions cover the type of prophylactic/reactive concomitant medication recommended by the treating physician, frequency of use, and the degree of impact on daily life due to use of the respective medication.	Up to approximately 60 Months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2025
• Primary Completion (Estimated): November 19, 2030
• Study Completion (Estimated): December 17, 2030

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 17, 2025

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 61186372NSC4014 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No