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 (COCOON)

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

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 and with modified enhanced dermatologic 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. The study also includes Expansion cohorts (in 2 different schedules) to evaluate enhanced dermatologic management and early intervention for DAEIs or paronychia, in participants receiving subcutaneous 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Lazertinib; Drug: Doxycycline; Drug: Minocycline; Drug: Clindamycin; Drug: Chlorhexidine; Other: Noncomedogenic skin moisturizer; Drug: Amivantamab SC; Drug: Amivantamab IV; Other: Ruxolitinib; Other: Tacrolimus; Drug: Zinc gluconate; Drug: Propranolol; Drug: Timolol; Drug: Clobetasol

• Study Type: Interventional
• Enrollment (Actual): 305
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1199
    • Hospital Italiano de Buenos Aires
  • CABA, Argentina, C1122
    • IADT Instituto Argentino de Diagnostico y Tratamiento
  • Capital Federal, Argentina, C1017
    • Centro Medico Austral
  • La Plata, Argentina, B1900AXI
    • Hospital Italiano de La Plata
  • Mar del Plata, Argentina, B7602
    • Hospital Privado de La Comunidad
• Brazil
  • Belo Horizonte, Brazil, 30150-221
    • Santa Casa de Misericordia de Belo Horizonte
  • Belém, Brazil, 66.073-005
    • CTO Centro de Tratamento Oncologico LTDA
  • Curitiba, Brazil, 81520-060
    • Liga Paranaense de Combate ao Cancer
  • Jaú, Brazil, 17.210-080
    • Fundação Doutor Amaral Carvalho
  • Porto Alegre, Brazil, 91350 200
    • Hospital Nossa Senhora da Conceicao S A
  • Salvador, Brazil, 40170 070
    • Nucleo de Oncologia da Bahia Oncoclinicas
  • Santa Cruz do Sul, Brazil, 96835-100
    • Hospital Ana Nery Santa Cruz do Sul
  • São Paulo, Brazil, 01509 900
    • Fundacao Antonio Prudente A C Camargo Cancer Center
  • São Paulo, Brazil, 01246 000
    • Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo
  • Taubaté, Brazil, 12030-200
    • Servicos de Tratamento ao Cancer de Taubate LTDA - Instituto do Cancer Brasil Unidade Taubate
  • Vitória, Brazil, 29043-260
    • Associacao Feminina de Educacao e Combate ao Cancer Hospital Santa Rita de Cassia
• China
  • Changzhou, China, 213004
    • Changzhou No 2 Peoples Hospital
  • Chengdoucun, China, 610041
    • West China Hospital
  • Chengdu, China, 610041
    • Sichuan Cancer Hospital
  • Guangzhou, China, 510080
    • The First Affiliated Hospital Sun Yat sen University
  • Hangzhou, China, 310003
    • The First Affiliated Hospital Zhejiang University School Of Medicine
  • Harbin, China, 150040
    • Harbin Medical University Cancer Hospital
  • Huizhou, China, 516001
    • Huizhou Municipal Central Hospital
  • Nanjing, China, 210000
    • Zhongda Hospital Southeast University
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Xi'an, China, 710061
    • The First Affiliated Hospital of Xian Jiaotong University
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• France
  • Marseille, France, 13915
    • Hopital Nord
  • Nice, France, 06001
    • Hôpital Pasteur
  • Paris, France, 75005
    • Institut Curie
• Germany
  • Aachen, Germany, 52074
    • Universitaetsklinikum der RWTH Aachen
  • Essen, Germany, 45136
    • Kliniken Essen-Mitte
  • Giessen, Germany, 35392
    • Universitaetsklinikum Giessen Und Marburg Gmbh
  • Heidelberg, Germany, 69126
    • Thoraxklinik am Universitatsklinikum Heidelberg
  • Kassel, Germany, 34125
    • Klinikum Kassel Gmbh
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig Holstein Campus Kiel
• Malaysia
  • George Town, Malaysia, 10450
    • Hospital Pulau Pinang
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
  • Kuantan, Malaysia, 25100
    • Hospital Tengku Ampuan Afzan
  • Kuching, Malaysia, 93586
    • Hospital Umum Sarawak
• South Korea
  • Cheongju-si, South Korea, 28644
    • Chungbuk National University Hospital
  • Incheon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System
• Spain
  • A Coruña, Spain, 15006
    • Hosp Univ A Coruna
  • Alicante, Spain, 03010
    • Hosp. Gral. Univ. de Alicante
  • Barcelona, Spain, 08028
    • Hosp. Univ. Quiron Dexeus
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Jaén, Spain, 23007
    • Hosp. Univ. de Jaen
  • Lugo, Spain, 27003
    • Hosp. Univ. Lucus Augusti
  • Madrid, Spain, 28007
    • Hosp. Gral. Univ. Gregorio Maranon
  • Málaga, Spain, 29010
    • Hosp Regional Univ de Malaga
  • Seville, Spain, 41014
    • Hosp. Ntra. Sra. de Valme
• Taiwan
  • Hsinchu, Taiwan, 30059
    • National Taiwan University Hospital Hsin Chu Branch
  • Kaohsiung City, Taiwan, 833
    • Chang Gung Memorial Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taoyuan City, Taiwan, 333
    • Linkou Chang Gung Memorial Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 1060
    • Adana City Hospital
  • Ankara, Turkey (Türkiye), 06560
    • Gazi University Hospital
  • Ankara, Turkey (Türkiye), 06010
    • Gulhane Training and Research Hospital
  • Ankara, Turkey (Türkiye), 6800
    • Ankara Bilkent City Hospital
  • Istanbul, Turkey (Türkiye), 34147
    • Bakirkoy Training and Research Hospital
  • Istanbul, Turkey (Türkiye), 34295
    • I A U VM Medical Park Florya Hastanesi
  • Izmir, Turkey (Türkiye), 35100
    • Ege University Medical Faculty
  • Samsun, Turkey (Türkiye), 55420
    • Ondokuz Mayis University
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Fullerton, California, United States, 92835
      • Providence Fullerton
    • Glendale, California, United States, 91204
      • Los Angeles Cancer Network
    • Huntington Beach, California, United States, 92648
      • City of Hope Seacliff
    • Irvine, California, United States, 92618
      • City of Hope Orange County Lennar Foundation Cancer Center
    • Long Beach, California, United States, 90813
      • City of Hope Long Beach Elm
    • Los Alamitos, California, United States, 90720
      • Cancer and Blood Specialty Clinic
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
    • Newport Beach, California, United States, 92663
      • USC Norris Oncology Hematology Newport Beach
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland Medical Center
    • Roseville, California, United States, 95661
      • Kaiser Permanente Roseville Medical Center
    • San Francisco, California, United States, 94115
      • Kaiser Permanente San Francisco Medical Center
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Santa Clara Medical Center
    • South Pasadena, California, United States, 91030
      • City of Hope South Pasadena
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Northern California
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente Walnut Creek Medical Center
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Hope And Healing Care
  • Missouri
    • Springfield, Missouri, United States, 65807
      • Oncology Hematology Associates
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Health Medical Oncology
  • New Jersey
    • Flemington, New Jersey, United States, 08822
      • Hunterdon Hematology Oncology
  • New York
    • Westbury, New York, United States, 11590
      • Clinical Research Alliance Inc
  • North Carolina
    • Wilson, North Carolina, United States, 27893
      • Regional Medical Oncology Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Renton, Washington, United States, 98055
      • Valley Medical Center
  • Wisconsin
    • West Salem, Wisconsin, United States, 54669
      • Gundersen Health System

Participation Criteria

Eligibility Criteria

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

Description

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). For the amivantamab SC expansion cohorts: Due to the increased risk of skin cancer with ruxolitinib, participants with any prior or concurrent skin malignancies will be excluded
• 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). For the amivantamab SC expansion cohorts, this includes active localized serious infections; 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, timolol*, ruxolitinib*, zinc*, corticosteroids* or their excipients or to any component of the enhanced dermatologic management (*for the amivantamab SC expansion cohorts)
• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Enhanced Dermatologic Management; Participants will receive enhanced dermatologic management to reduce toxicities in skin and nail with doxycycline tablet or minocycline capsule, clindamycin topical lotion, chlorhexidine topical solution, and noncomedogenic skin moisturizer during background anticancer treatment of advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with amivantamab intravenously (Dose 1 for body weight [BW] less than 80 kilograms [kg] and Dose 2 for BW greater than or equal to [>=] 80 kg as IV infusion [Arm A]) until documented disease progression using Response Evaluation Criteria in Solid Tumors version 1.1).	Drug: Lazertinib; Lazertinib tablet will be administered orally.; Other Names: JNJ-73841937; Drug: Doxycycline; Doxycycline tablet will be administered orally.; Drug: Minocycline; Minocycline capsule will be administered orally.; Drug: Clindamycin; Clindamycin lotion will be used as topical application on the scalp.; Drug: Chlorhexidine; Chlorhexidine solution will be used as topical application on hands and feet.; Other: Noncomedogenic skin moisturizer; Noncomedogenic skin moisturizer will be used as topical application.; Drug: Amivantamab IV; Amivantamab will be administered.; Other Names: JNJ-61186372
Active Comparator: Arm B: Standard-of-Care Dermatologic Management; Participants will receive standard care for dermatologic management according to local practice to reduce dermatologic toxicities in skin and nail during background anticancer treatment of advanced or metastatic EGFR-mutated NSCLC with amivantamab administered as IV infusion plus lazertinib, dose and dosing schedule as same as experimental arm.	Drug: Lazertinib; Lazertinib tablet will be administered orally.; Other Names: JNJ-73841937; Drug: Chlorhexidine; Chlorhexidine solution will be used as topical application on hands and feet.; Other: Noncomedogenic skin moisturizer; Noncomedogenic skin moisturizer will be used as topical application.; Drug: Amivantamab IV; Amivantamab will be administered.; Other Names: JNJ-61186372
Experimental: Sub-study: Cohort A: Ruxolitinib; Participants enrolled in Arms A and B of the main study who experience new-onset or persistent specific DAEIs (Grade greater than or equal to [>=] 2, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0) will be enrolled and receive reactive treatment with ruxolitinib in the sub-study. Participants in the sub-study will continue to receive amivantamab and lazertinib.	Drug: Lazertinib; Lazertinib tablet will be administered orally.; Other Names: JNJ-73841937; Drug: Doxycycline; Doxycycline tablet will be administered orally.; Drug: Minocycline; Minocycline capsule will be administered orally.; Drug: Clindamycin; Clindamycin lotion will be used as topical application on the scalp.; Drug: Chlorhexidine; Chlorhexidine solution will be used as topical application on hands and feet.; Other: Noncomedogenic skin moisturizer; Noncomedogenic skin moisturizer will be used as topical application.; Drug: Amivantamab IV; Amivantamab will be administered.; Other Names: JNJ-61186372; Other: Ruxolitinib; Ruxolitinib will be used to the affected skin area.
Experimental: Sub-study: Cohort B: Tacrolimus; Participants enrolled in Arms A and B of the main study who experience new-onset or persistent specific DAEIs (Grade >= 2, as defined by NCI-CTCAE v5.0) will be enrolled and receive reactive treatment with tacrolimus in the sub-study. Participants in the sub-study will continue to receive amivantamab and lazertinib.	Drug: Lazertinib; Lazertinib tablet will be administered orally.; Other Names: JNJ-73841937; Drug: Doxycycline; Doxycycline tablet will be administered orally.; Drug: Minocycline; Minocycline capsule will be administered orally.; Drug: Clindamycin; Clindamycin lotion will be used as topical application on the scalp.; Drug: Chlorhexidine; Chlorhexidine solution will be used as topical application on hands and feet.; Other: Noncomedogenic skin moisturizer; Noncomedogenic skin moisturizer will be used as topical application.; Drug: Amivantamab IV; Amivantamab will be administered.; Other Names: JNJ-61186372; Other: Tacrolimus; Tacrolimus will be used as topical application to the affected skin area.
Experimental: Amivantamab Subcutaneous (SC) Expansion Cohort: Standard Schedule; Participants will receive modified enhanced dermatologic management with oral doxycycline or minocycline, zinc gluconate and noncomedogenic skin moisturizer during background anticancer treatment of advanced or metastatic EGFR mutated NSCLC with amivantamab SC and lazertinib as per standard schedule. If a participant develops a dermatologic adverse event of interest (DAEI) they will receive early intervention as follows: for facial (ruxolitinib), for scalp (oral propranolol and clobetasol), for paronychia (chlorhexidine in addition to timolol) until documented disease progression using Response Evaluation Criteria in Solid Tumors version 1.1.	Drug: Lazertinib; Lazertinib tablet will be administered orally.; Other Names: JNJ-73841937; Drug: Doxycycline; Doxycycline tablet will be administered orally.; Drug: Minocycline; Minocycline capsule will be administered orally.; Drug: Chlorhexidine; Chlorhexidine solution will be used as topical application on hands and feet.; Other: Noncomedogenic skin moisturizer; Noncomedogenic skin moisturizer will be used as topical application.; Drug: Amivantamab SC; Amivantamab will be administered as SC injection.; Other Names: JNJ-61186372; Other: Ruxolitinib; Ruxolitinib will be used to the affected skin area.; Drug: Zinc gluconate; Zinc gluconate tablet will be administered.; Drug: Propranolol; Propranolol tablet will be administered.; Drug: Timolol; Timolol will be used to the affected skin area.; Drug: Clobetasol; Clobetasol shampoo will be used on the scalp.
Experimental: Amivantamab SC Expansion Cohort: Modified Schedule; Participants will receive modified enhanced dermatologic management with oral doxycycline or minocycline, zinc gluconate and noncomedogenic skin moisturizer during background anticancer treatment of advanced or metastatic EGFR mutated NSCLC with amivantamab SC and lazertinib as per modified schedule. If a participant develops a DAEI they will receive early intervention as follows: for facial (ruxolitinib), for scalp (oral propranolol and clobetasol), for paronychia (chlorhexidine in addition to timolol) until documented disease progression using Response Evaluation Criteria in Solid Tumors version 1.1.	Drug: Lazertinib; Lazertinib tablet will be administered orally.; Other Names: JNJ-73841937; Drug: Doxycycline; Doxycycline tablet will be administered orally.; Drug: Minocycline; Minocycline capsule will be administered orally.; Drug: Amivantamab SC; Amivantamab will be administered as SC injection.; Other Names: JNJ-61186372

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Number of participants with Grade >= 2 DAEIs within 12 weeks after initiation of anticancer treatment based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0 will be reported. DAEIs includes rash, dermatitis acneiform, pruritus, skin fissures, acne, folliculitis, erythema, eczema, rash maculo-papular, skin exfoliation, skin lesion, skin irritation, dermatitis, rash erythematous, rash macular, rash popular, rash pruritic, rash pustular, dermatitis contact, dermatitis exfoliative generalized, drug eruption, dyshidrotic eczema, eczema asteatotic and paronychia. As per NCI CTCAE v 5.0, severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event.	Up to 12 weeks after initiation of anticancer treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Occurrence of Grade >=2 DAEI	Time to first occurrence of Grade >=2 DAEI will be reported.	Up to 12 months
Change From Baseline in Skindex Symptoms Domain Score up to 12 Months	Change from baseline in skindex symptoms domain score up to 12 months will be reported. The score of quality of life will be assessed using the Skindex-16 questionnaire. Skindex-16 is used for participants to rate skin conditions.	Baseline, up to Month 12
Change From Baseline in Patient's Global Impression-Severity (PGI-S) Rash up to 12 Months	Change from baseline in PGI-S rash up to 12 months will be reported. Participant quality of life will be evaluated using PGI-S Rash. PGI-S is a single-item questionnaire assessing participants disease severity on a 7-point response scale.	Baseline, up to Month 12
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	Change from baseline in EORTC-QLQ-C30 score up to 12 months will be reported. EORTC-QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies.	Baseline, up to Month 12
Percentage of Participants With Dose Reductions, Dose Interruptions, and Dose Discontinuations of Anticancer Treatment due to DAEIs	Percentage of participants with dose reductions, dose interruptions, and dose discontinuations of anticancer treatment due to DAEIs will be reported.	Up to 12 months
Relative Dose Intensity (RDI) of Anticancer Treatment	Relative dose intensity of anticancer treatment will be reported. The relative dose intensity is defined as the ratio of total actually received dose versus total prescribed dose.	Up to 12 months
Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause, whichever occurs first.	Up to 12 months
Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve a partial response (PR) or better response using RECIST v1.1 as assessed by the investigator.	Up to 12 months
Duration of Response (DoR)	DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the RECIST v1.1 response criteria.	Up to 12 months
Number of Grade >= 2 DAEI Per Participants	Number of grade >= 2 DAEI per participants will be reported.	Up to 12 months
Time to Resolution of Grade >= 2 DAEI	Time to resolution of Grade >= 2 DAEI will be reported.	Up to 12 months
Change From Baseline in EuroQol 5 - Dimension (EQ-5D) Patient-reported Outcome (PRO) up to 12 Months (for Amivantamab Subcutaneous Expansion Cohort Only)	The EQ-5D questionnaire is a brief, generic HRQOL assessment that can that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening. EQ-5D scores include EQ-5D valuation index score (a weighted scoring of the 5 dimension scores with a possible range from 0 to 1), EQ-5D visual analog scale (VAS) is a vertical VAS with scores ranging from 0 (worst imaginable health) to 100 (perfect health), and EQ5D descriptive system scores (five scores reflecting each of the 5 EQ-5D health dimensions ranging from 0 [no limitation] to 4 [incapacity]).	Baseline, up to Month 12
Number of Participants With DAEIs by Severity Based on NCI-CTCAE v 5.0	Number of participants with DAEIs by severity based on NCI-CTCAE v 5.0 will be reported.	Up to 12 weeks after initiation of anticancer treatment
Number of Participants With Grade >=2 DAEIs Within 6 Months After Initiation of Anticancer Treatment Based on NCI-CTCAE v 5.0	Number of participants with Grade >=2 DAEIs within 6 months after initiation of anticancer treatment based on NCI-CTCAE v 5.0 will be reported.	Up to 6 months after initiation of anticancer treatment
Number of Participants With Paronychia by Severity Based on NCI-CTCAE v 5.0	Number of participants with paronychia by severity based on NCI-CTCAE v 5.0 will be reported.	Up to 6 months after initiation of anticancer treatment
Number of Participants With Scalp Rash by Severity Based on NCI-CTCAE v 5.0	Number of participants with scalp rash by severity based on NCI-CTCAE v 5.0 will be reported.	Up to 12 months after initiation of anticancer treatment
Percentage of Participants With Venous Thromboembolism (VTE) Adverse Events (AEs) by Severity Based on NCI-CTCAE v 5.0	Percentage of participants with VTE AEs (pulmonary embolism and deep vein thrombosis) by severity based on NCI-CTCAE v 5.0 will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.	Up to 12 months
Percentage of Participants With Adverse Events (AEs) by Severity Based on NCI-CTCAE v 5.0	Percentage of participants with AEs by severity based on NCI-CTCAE v 5.0 will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.	Up to 12 months
Amivantamab SC Expansion Cohorts: Number of Participants With Grade >= 2 DAEIs Within 12 Weeks After Initiation of Anticancer Treatment	Participants with Grade >= 2 DAEIs within 12 weeks after initiation of anticancer treatment based on NCI-CTCAE v 5.0 will be reported. DAEIs includes rash, dermatitis acneiform, pruritus, skin fissures, acne, folliculitis, erythema, eczema, rash maculo-papular, skin exfoliation, skin lesion, skin irritation, dermatitis, rash erythematous, rash macular, rash popular, rash pruritic, rash pustular, dermatitis contact, dermatitis exfoliative generalized, drug eruption, dyshidrotic eczema, eczema asteatotic and paronychia. As per NCI-CTCAE v 5.0, severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event.	Up to 12 weeks after initiation of anticancer treatment
Amivantamab SC Expansion Cohorts: Percentage of Participants With an Improvement in DAEI After Starting Early Intervention	Percentage of participants showing an improvement in DAEI by a minimum of 1 NCI-CTCAE grade after starting early intervention will be reported. As per NCI-CTCAE v 5.0, severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event.	Up to 12 months
Amivantamab SC Expansion Cohorts: Time to Improvement of DAEIs After Starting Early Intervention	Time to improvement of DAEIs by a minimum of 1 NCI-CTCAE grade after starting early intervention will be reported. As per NCI-CTCAE v 5.0, severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event.	Up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Best Response for the Dermatologic Adverse Event	Participants achieving best response within 12 weeks of treatment defined as NCI-CTCAE level of the dermatologic adverse event improvement by at least 1 level will be reported.	Up to 12 weeks

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Cho BC, Li W, Spira AI, Sauder M, Feldman J, Bozorgmehr F, Mak M, Smith J, Voon PJ, Liu B, Tian P, Tan JL, Yang CT, Shih JY, Karadurmus N, Cundom JE, Bertollo G, Cicin I, Nieva J, Ortega-Granados AL, Tomasini P, Nguyen D, Felip E, Schuchard J, Murphy SP, Anderson BG, Romero T, Xia Y, Sheng S, Bauml JM, Mahadevia PJ, Kam J, Nematian-Samani M, Simoes J, Wildgust M, Girard N. Enhanced Versus Standard Dermatologic Management With Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC: The COCOON Global Randomized Controlled Trial. J Thorac Oncol. 2025 Oct;20(10):1517-1530. doi: 10.1016/j.jtho.2025.07.117. Epub 2025 Sep 9.

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): January 31, 2032

Study Registration Dates

• First Submitted: November 2, 2023
• First Submitted That Met QC Criteria: November 2, 2023
• First Posted (Actual): November 7, 2023

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; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Amines; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Alcohols; Macrolides; Lactones; Naphthacenes; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Pyrrolidines; Tetracyclines; Lincomycin; Lincosamides; Biguanides; Guanidines; Amidines; Thiadiazoles; Morpholines; Oxazines; Betamethasone; Minocycline; Doxycycline; Tacrolimus; Chlorhexidine; Clindamycin; Timolol; Propranolol; Clobetasol; amivantamab; lazertinib; ruxolitinib; gluconic acid
• Other Study ID Numbers: 61186372NSC2007 (Other Identifier: Janssen Research & Development, LLC); 2023-505863-35-00 (Registry Identifier: EUCT number)

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