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Active, not recruiting Phase 2

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

NCT06120140 · tracked via the Priya Life Science Spain tracker
Phase
Phase 2
Started
2024-02-16
Last updated
2026-09-25

Condition(s) studied

Carcinoma, Non-Small-Cell Lung

Investigational drug(s) / intervention(s)

Amivantamab IV →Amivantamab SC →Lazertinib →Doxycycline →Minocycline →Clindamycin →Chlorhexidine →Noncomedogenic skin moisturizerRuxolitinibTacrolimusZinc gluconatePropranolol →TimololClobetasol →

Amivantamab IV: Amivantamab will be administered.

Amivantamab SC: Amivantamab will be administered as SC injection.

Lazertinib: Lazertinib tablet will be administered orally.

Doxycycline: Doxycycline tablet will be administered orally.

Minocycline: Minocycline capsule will be administered orally.

Clindamycin: Clindamycin lotion will be used as topical application on the scalp.

Chlorhexidine: Chlorhexidine solution will be used as topical application on hands and feet.

Noncomedogenic skin moisturizer: Noncomedogenic skin moisturizer will be used as topical application.

Ruxolitinib: Ruxolitinib will be used to the affected skin area.

Tacrolimus: Tacrolimus will be used as topical application to the affected skin area.

Zinc gluconate: Zinc gluconate tablet will be administered.

Propranolol: Propranolol tablet will be administered.

Timolol: Timolol will be used to the affected skin area.

Clobetasol: Clobetasol shampoo will be used on the scalp.

Study 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 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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)

Primary outcome measure(s)

  • 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 — Up to 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.

Trial sites (93)

FacilityCityRegionStatus
Ironwood Cancer and Research Center Chandler Arizona
City of Hope Duarte California
Providence Fullerton Fullerton California
Los Angeles Cancer Network Glendale California
City of Hope Seacliff Huntington Beach California
City of Hope Orange County Lennar Foundation Cancer Center Irvine California
City of Hope Long Beach Elm Long Beach California
Cancer and Blood Specialty Clinic Los Alamitos California
Keck Hospital of USC Los Angeles California
USC Norris Oncology Hematology Newport Beach Newport Beach California
Kaiser Permanente Oakland Medical Center Oakland California
Kaiser Permanente Roseville Medical Center Roseville California
Kaiser Permanente San Francisco Medical Center San Francisco California
Kaiser Permanente Santa Clara Medical Center Santa Clara California
City of Hope South Pasadena South Pasadena California
Kaiser Permanente Northern California Vallejo California
Kaiser Permanente Walnut Creek Medical Center Walnut Creek California
University Cancer & Blood Center Athens Georgia
Hope and Healing Care Hinsdale Illinois
Oncology Hematology Associates Springfield Missouri
Renown Health Medical Oncology Reno Nevada
Hunterdon Hematology Oncology Flemington New Jersey
Clinical Research Alliance Inc Westbury New York
Regional Medical Oncology Center Wilson North Carolina
University Hospitals Cleveland Medical Center Cleveland Ohio
Virginia Cancer Specialists Fairfax Virginia
Valley Medical Center Renton Washington
Gundersen Health System West Salem Wisconsin
Hospital Italiano de Buenos Aires Buenos Aires Argentina
IADT Instituto Argentino de Diagnostico y Tratamiento CABA Argentina
Centro Medico Austral Capital Federal Argentina
Hospital Italiano de La Plata La Plata Argentina
Hospital Privado de la Comunidad Mar del Plata Argentina
CTO Centro De Tratamento Oncologico LTDA Belém Brazil
Santa Casa de Misericordia de Belo Horizonte Belo Horizonte Brazil
Liga Paranaense de Combate ao Cancer Curitiba Brazil
Fundacao Doutor Amaral Carvalho Jaú Brazil
Hospital Nossa Senhora da Conceicao S A Porto Alegre Brazil
Nucleo de Oncologia da Bahia Oncoclinicas Salvador Brazil
Hospital Ana Nery Santa Cruz do Sul Santa Cruz do Sul Brazil

+ 53 more sites — see the full list on the official registry below.

Official registry record

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 NCT06120140 on ClinicalTrials.gov ↗ ← All trials in Spain