Resumen

El propósito de este estudio es evaluar si el manejo dermatológico intensificado puede reducir la incidencia de eventos adversos dermatológicos de interés (EADI) de grado mayor o igual a (\>=) 2 en comparación con el manejo cutáneo estándar y con el manejo dermatológico intensificado modificado en participantes con cáncer de pulmón de células no pequeñas (NSCLC) localmente avanzado o metastásico en estadio IIIB/C-IV con mutación del receptor del factor de crecimiento epidérmico (EGFR), tratados en primera línea con amivantamab y lazertinib. El estudio también incluye cohortes de expansión (en 2 esquemas diferentes) para evaluar el manejo dermatológico intensificado y la intervención temprana para EADI o paroniquia en participantes que reciben amivantamab subcutáneo y lazertinib. Un subestudio reclutará participantes de los brazos A y B que experimenten EADI de nueva aparición o persistentes específicos (grado \>=2) durante el tratamiento con amivantamab intravenoso (IV) y lazertinib. Este subestudio tiene como objetivo evaluar el uso reactivo de estrategias de tratamiento dermatológico en estos participantes.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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)

Criterios de exclusión

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)

Intervenciones

drug

Amivantamab IV

Amivantamab will be administered.

drug

Amivantamab SC

Amivantamab will be administered as SC injection.

drug

Lazertinib

Lazertinib tablet will be administered orally.

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.

other

Ruxolitinib

Ruxolitinib will be used to the affected skin area.

other

Tacrolimus

Tacrolimus will be used as topical application 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.

Ubicaciones

Hospital Italiano de Buenos Aires

Buenos Aires, Argentina

RECRUITING

IADT Instituto Argentino de Diagnostico y Tratamiento

CABA, Argentina

RECRUITING

Centro Medico Austral

Capital Federal, Argentina

RECRUITING

Hospital Italiano de La Plata

La Plata, Argentina

COMPLETED

Hospital Privado de la Comunidad

Mar del Plata, Argentina

RECRUITING

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Amivantamab IV

Amivantamab SC

Lazertinib

Doxycycline

Minocycline

Clindamycin

Chlorhexidine

Noncomedogenic skin moisturizer

Ruxolitinib

Tacrolimus

Zinc gluconate

Propranolol

Timolol

Clobetasol

Ubicaciones

Hospital Italiano de Buenos Aires

IADT Instituto Argentino de Diagnostico y Tratamiento

Centro Medico Austral

Hospital Italiano de La Plata

Hospital Privado de la Comunidad

Patrocinadores

Contactos

Study Contact