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

Inclusion Criteria:

• Have histologically or cytologically confirmed, locally advanced or metastaticnon-small cell lung cancer (NSCLC); Is treatment naive and not amenable to curativetherapy including surgical resection or (chemo) radiation. Adjuvant or neoadjuvanttherapy for Stage I, Stage II or Stage IIIA disease is allowed if last doseadministered more than 12 months prior to the development of locally advanced ormetastatic disease

• Have a tumor that harbors an epidermal growth factor receptor (EGFR) Exon 19del orExon 21 L858R substitution, as detected by an Food and Drug Administration (FDA)-approved or other validated test in a clinical laboratory improvementamendments (CLIA)-certified laboratory (sites in the United States) or an accreditedlocal laboratory (sites outside of the United States) in accordance with sitestandard-of-care

• A participant with asymptomatic or previously treated and stable brain metastasesmay participate in this study. Participants with a history of symptomatic brainmetastases must have had all lesions treated as clinically indicated (that is, nocurrent indication for further definitive local therapy). Any definitive localtherapy to brain metastases must have been completed at least 14 days prior torandomization, 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 studyendpoints, safety, or the efficacy of the study treatment(s). For the amivantamab SCexpansion 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-responsiveto standard of care [SoC]) Grade >=2 specific DAEIs of the scalp, face, or body, asdefined 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 withantimicrobial therapy [participants will be required to complete antibiotics 1 weekprior to starting background anticancer treatment] or diagnosed or suspected viralinfection). For the amivantamab SC expansion cohorts, this includes active localizedserious infections; active bleeding diathesis; impaired oxygenation requiringcontinuous oxygen supplementation; refractory nausea and vomiting, chronicgastrointestinal diseases, inability to swallow the formulated product, or previoussignificant bowel resection that would preclude adequate absorption of backgroundanticancer treatment or doxycycline/minocycline; psychiatric illness, socialsituation, or any other circumstances that would limit compliance with studyrequirements; any ophthalmologic condition that is clinically unstable; pre-existingskin condition that would prevent adequate evaluations of dermatologic toxicity, asdetermined by the investigator

• Medical history of interstitial lung disease (ILD), including drug-induced ILD orradiation 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 enhanceddermatologic management (*for the amivantamab SC expansion cohorts)

• Participant has received any prior systemic treatment at any time for locallyadvanced stage III B/C or metastatic stage IV disease (adjuvant or neoadjuvanttherapy for stage I, II or IIIA disease is allowed if last dose administered morethan 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 growthfactor receptor (EGFR)-induced DAEIs with JAK inhibitors (for Cohort A) orcalcineurin inhibitors (for Cohort B)