Clinical trial NCT06120140: Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib
Official title: A Phase 2, Open-Label, Randomized Trial Evaluating the Impact of Enhanced Versus Standard Dermatologic Management on Selected Dermatologic Adverse Events Among Patients With Locally Advanced or Metastatic EGFR-Mutated NSCLC Treated First-Line With Amivantamab + Lazertinib
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2023-11-07
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate whether enhanced dermatologic management can reduce incidence of grade greater than or equal to (\>=) 2 dermatologic adverse events of interest (DAEIs) when compared with standard-of-care skin management in participants with locally advanced or metastatic stage IIIB/C-IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated first-line with amivantamab and lazertinib. A substudy will enroll participants from Arms A and B who experience specific new-onset or persistent DAEIs (Grade \>=2) during treatment with intravenous (IV) amivantamab and lazertinib. This substudy aims to assess the reactive use of dermatologic treatment strategies in these participants.


Eligibility criteria: Inclusion Criteria:

* Have histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC); Is treatment naive and not amenable to curative therapy including surgical resection or (chemo) radiation. Adjuvant or neoadjuvant therapy for Stage I, Stage II or Stage IIIA disease is allowed if last dose administered more than 12 months prior to the development of locally advanced or metastatic disease
* Have a tumor that harbors an epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution, as detected by an Food and Drug Administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA)-certified laboratory (sites in the United States) or an accredited local laboratory (sites outside of the United States) in accordance with site standard of care
* A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants with a history of symptomatic brain metastases must have had all lesions treated as clinically indicated (that is, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization, and the participant can be receiving no greater than 10 milligram (mg) prednisone or equivalent daily for the treatment of intracranial disease
* Can have prior or concurrent second malignancy (other than the disease under study)which natural history or treatment is unlikely to interfere with any study endpoints, safety, or the efficacy of the study treatment(s)
* Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1
* Sub-study: Participants must have new-onset or persistent (defined as non-responsive to standard of care \[SoC\]) Grade \>=2 specific DAEIs of the scalp, face, or body, as defined by NCI CTCAE Grading v5.0 for DAEIs (excluding paronychia)

Exclusion Criteria:

* History of uncontrolled illness, including but not limited to uncontrolled diabetes; ongoing or active infection (includes infection requiring treatment with antimicrobial therapy \[participants will be required to complete antibiotics 1 week prior to starting background anticancer treatment\] 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 background anticancer treatment or doxycycline/minocycline; psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements; any ophthalmologic condition that is clinically unstable; pre-existing skin condition that would prevent adequate evaluations of dermatologic toxicity, as determined by the investigator
* Medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
* Known allergy, hypersensitivity, or intolerance to the excipients of amivantamab, lazertinib, or to tetracyclines, doxycycline, minocycline, or their excipients or to any component of the enhanced dermatologic management
* Participant has received any prior systemic treatment at any time for locally advanced stage III B/C or metastatic stage IV disease (adjuvant or neoadjuvant therapy for stage I, II or IIIA disease is allowed if last dose administered more than 12 months prior to the development of locally advanced or metastatic disease)
* Participant has an active or past medical history of leptomeningeal disease
* Sub-study: Participants who have received prior treatment for epidermal growth factor receptor (EGFR)-induced DAEIs with JAK inhibitors (for Cohort A) or calcineurin inhibitors (for Cohort B)

Primary outcomes:
measure: Number of Participants With Grade Greater Than or Equal to (>=) 2 Dermatologic Adverse Events of Interest (DAEIs) Within 12 Weeks After Initiation of Anticancer Treatment
timeFrame: Up to 12 weeks after initiation of anticancer treatment
Secondary outcomes:
measure: Number of Participants With DAEIs by Severity Based on NCI CTCAE v 5.0
timeFrame: Up to 12 weeks after initiation of anticancer treatment
measure: Number of Participants With Grade >=2 DAEIs Within 6 Months After Initiation of Anticancer Treatment Based on NCI CTCAE v 5.0
timeFrame: Up to 6 months after initiation of anticancer treatment
measure: Number of Grade >= 2 DAEI Per Participants
timeFrame: Up to 12 months
measure: Time to First Occurrence of Grade >=2 DAEI
timeFrame: Up to 12 months
measure: Time to Resolution of Grade >= 2 DAEI
timeFrame: Up to 12 months
measure: Number of Participants With Paronychia by Severity Based on NCI CTCAE v 5.0
timeFrame: Up to 6 months after initiation of anticancer treatment
measure: Number of Participants With Scalp Rash by Severity Based on NCI CTCAE v 5.0
timeFrame: Up to 12 months after initiation of anticancer treatment
measure: Change From Baseline in Skindex Symptoms Domain Score up to 12 Months
timeFrame: Baseline, up to Month 12
measure: Change From Baseline in Patient's Global Impression-Severity (PGI-S) Rash up to 12 Months
timeFrame: Baseline, up to Month 12
measure: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score up to 12 Months
timeFrame: Baseline, up to Month 12
measure: Change From Baseline in EuroQol 5 - Dimension (EQ-5D) Patient-reported Outcome (PRO) up to 12 Months (for Amivantamab Subcutaneous Expansion Cohort Only)
timeFrame: Baseline, up to Month 12
measure: Percentage of Participants With Dose Reductions, Dose Interruptions, and Dose Discontinuations of Anticancer Treatment due to DAEIs
timeFrame: Up to 12 months
measure: Relative Dose Intensity (RDI) of Anticancer Treatment
timeFrame: Up to 12 months
measure: Percentage of Participants With Venous Thromboembolism (VTE) Adverse Events (AEs) by Severity Based on NCI CTCAE v 5.0
timeFrame: Up to 12 months
measure: Percentage of Participants With Adverse Events (AEs) by Severity Based on NCI CTCAE v 5.0
timeFrame: Up to 12 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 12 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 12 months
measure: Duration of Response (DoR)
timeFrame: Up to 12 months
Other outcomes:
measure: Percentage of Participants Achieving Best Response for the Dermatologic Adverse Event
timeFrame: Up to 12 weeks
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Fullerton
country: United States
facility: Providence Fullerton
state: California
city: Glendale
country: United States
facility: Los Angeles Cancer Network
state: California
city: Huntington Beach
country: United States
facility: City of Hope Seacliff
state: California
city: Irvine
country: United States
facility: City of Hope Orange County Lennar Foundation Cancer Center
state: California
city: Long Beach
country: United States
facility: City of Hope Long Beach Elm
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Newport Beach
country: United States
facility: USC Norris Oncology Hematology Newport Beach
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland Medical Center
state: California
city: Roseville
country: United States
facility: Kaiser Permanente Roseville Medical Center
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco Medical Center
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Santa Clara Medical Center
state: California
city: South Pasadena
country: United States
facility: City of Hope South Pasadena
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Northern California
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente Walnut Creek Medical Center
state: California
city: Athens
country: United States
facility: University Cancer & Blood Center
state: Georgia
city: Hinsdale
country: United States
facility: Hope and Healing Care
state: Illinois
city: Springfield
country: United States
facility: Oncology Hematology Associates
state: Missouri
city: Reno
country: United States
facility: Renown Health Medical Oncology
state: Nevada
city: Flemington
country: United States
facility: Hunterdon Hematology Oncology
state: New Jersey
city: Westbury
country: United States
facility: Clinical Research Alliance Inc
state: New York
city: Wilson
country: United States
facility: Regional Medical Oncology Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Renton
country: United States
facility: Valley Medical Center
state: Washington
city: W. Salem
country: United States
facility: Gundersen Health System
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Caba
country: Argentina
facility: IADT Instituto Argentino de Diagnostico y Tratamiento
city: Capital Federal
country: Argentina
facility: Centro Medico Austral
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
city: Mar del Plata
country: Argentina
facility: Hospital Privado de la Comunidad
city: Belem
country: Brazil
facility: CTO Centro De Tratamento Oncologico LTDA
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
city: Curitiba
country: Brazil
facility: Liga Paranaense de Combate ao Cancer
city: Jaú
country: Brazil
facility: Fundacao Doutor Amaral Carvalho
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao S A
city: Salvador
country: Brazil
facility: Nucleo de Oncologia da Bahia Oncoclinicas
city: Santa Cruz do Sul
country: Brazil
facility: Hospital Ana Nery Santa Cruz do Sul
city: Sao Paulo
country: Brazil
facility: Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo
city: Sao Paulo
country: Brazil
facility: Fundacao Antonio Prudente A C Camargo Cancer Center
city: Taubate
country: Brazil
facility: Servicos de Tratamento ao Cancer de Taubate LTDA - Instituto do Cancer Brasil Unidade Taubate
city: Vitoria
country: Brazil
facility: Associacao Feminina de Educacao e Combate ao Cancer Hospital Santa Rita de Cassia
city: Changzhou
country: China
facility: Changzhou No 2 Peoples Hospital
city: Chengdou
country: China
facility: West China Hospital
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
city: Guang Zhou
country: China
facility: The First Affiliated Hospital Sun Yat sen University
city: Hangzhou
country: China
facility: The First Affiliated Hospital Zhejiang University School of Medicine
city: Harbin
country: China
facility: Harbin medical university cancer hospital
city: Huizhou
country: China
facility: Huizhou Municipal Central Hospital
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
city: ShangHai
country: China
facility: Fudan University Shanghai Cancer Center
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Marseille Cedex 20
country: France
facility: Hopital Nord
city: Nice
country: France
facility: Hopital PASTEUR
city: Paris
country: France
facility: Institut Curie
city: Aachen
country: Germany
facility: Universitaetsklinikum der RWTH Aachen
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
city: Giessen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitatsklinikum Heidelberg
city: Kassel
country: Germany
facility: Klinikum Kassel GmbH
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig Holstein Campus Kiel
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Georgetown
country: Malaysia
facility: Hospital Pulau Pinang
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
city: A Coruna
country: Spain
facility: Hosp Univ A Coruna
city: Alicante
country: Spain
facility: Hosp. Gral. Univ. de Alicante
city: Barcelona
country: Spain
facility: Hosp. Univ. Quiron Dexeus
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Jaen
country: Spain
facility: Hosp. Univ. de Jaen
city: Lugo
country: Spain
facility: Hosp. Univ. Lucus Augusti
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Malaga
country: Spain
facility: Hosp Regional Univ de Malaga
city: Sevilla
country: Spain
facility: Hosp. Ntra. Sra. de Valme
city: Hsin Chu
country: Taiwan
facility: National Taiwan University Hospital Hsin Chu Branch
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Adana
country: Turkey
facility: Adana City Hospital
city: Ankara
country: Turkey
facility: Gulhane Training and Research Hospital
city: Ankara
country: Turkey
facility: Gazi University Hospital
city: Ankara
country: Turkey
facility: Ankara Bilkent City Hospital
city: Istanbul
country: Turkey
facility: Bakirkoy Training and Research Hospital
city: Istanbul
country: Turkey
facility: I A U VM Medical Park Florya Hastanesi
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayis University
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: