COCOON Study Design^3,4

COCOON (ClinicalTrials.gov Identifier: NCT06120140) enrollment period: February 2024 onwards; estimated study completion: March 31, 2026.
Abbreviations: AE, adverse event; APAC, Asia-Pacific; BID, twice daily; DAEI, dermatologic adverse event of interest; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; eGFR, estimated glomerular filtration rate; EU, European Union; Exon19del, Exon 19 deletion; ILD, interstitial lung disease; IV, intravenous; LATAM, Latin America; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NSCLC, non-small cell lung cancer; PO, orally; PRO, patient-reported outcome; QD, once daily; QW, once a week; Q2W, twice a week; R, randomization; SPF, sun protection factor; TKI, tyrosine kinase inhibitor; US, United States; W, week.
^aPatients must have had all lesions treated as clinically indicated and any definitive local therapy completed ≥2 weeks prior to randomization and are receiving no more than prednisone 10 mg (or equivalent) for treatment.
^beGFR >45 mL/min.
^cIncluding, but not limited to, uncontrolled diabetes, ongoing/active infection, active bleeding diathesis, impaired oxygenation requiring continuous oxygen supplementation, and psychiatric illness or other circumstances that would limit compliance with study requirements.
^dKnown allergy, hypersensitivity, or intolerance to the excipients of amivantamab or lazertinib; to tetracyclines, doxycycline, minocycline, or their excipients; or to any component of enhanced dermatologic management.
^eIncluding, but not limited to, deep vein thrombosis or pulmonary embolism within 1 month prior to administration of the first dose of background anticancer treatment or other cardiovascular diseases within 6 months prior to administration of the first dose.
^fAdjuvant/neoadjuvant therapy for stage I/II disease is allowed if administered >12 months prior to the development of locally advanced or metastatic disease.
^gAdjuvant treatment with osimertinib is allowed if administered >12 months prior to the development of locally advanced or metastatic disease and all osimertinib toxicities are resolved prior to enrollment.
^hThe planned enrollment of 180 patients (across the US, the EU, LATAM, and APAC) is estimated to provide 90% power (with a 2-sided alpha of 0.05) to detect a difference in the incidence of grade ≥2 dermatologic AEs between the 2 arms.
ⁱPatients will use a digital health tool to monitor treatment compliance.
^jAll patients will receive general skincare recommendations and will be eligible to receive additional dermatologic measures at the physician’s discretion.
^k1050 mg (1400 mg if body weight ≥80 kg) QW for the first 4 weeks and Q2W thereafter.
^lDAEIs include rash, dermatitis, paronychia, skin fissures, acne, erythema, skin exfoliation, skin lesion, skin irritation, and eczema.
^mAE severity per NCI CTCAE v5.0.