• Assess for signs/symptoms of venous thromboembolism such as PE (chest pain, dyspnea, tachycardia) or DVT (calf pain or tenderness, lower extremity edema, localized warmth or erythema). If Grade 2 or 3 thromboembolic event occurs, hold lazertinib and amivantamab; administer anticoagulant treatment as clinically indicated, then resume lazertinib and amivantamab at same dose. If Grade 4 or recurrent Grade 2 or 3 thromboembolic events occurs despite therapeutic level anticoagulation, hold lazertinib and permanently discontinue amivantamab; administer anticoagulant treatment as clinically indicated, then treatment can continue with lazertinib at same dose.
• Monitor for signs/symptoms of ILD or pneumonitis such as dyspnea, cough, hypoxia, fever. CT scan or chest x-ray can confirm. If ILD or pneumonitis suspected, hold lazertinib. If ILD or pneumonitis confirmed, permanently discontinue lazertinib.
• Monitor for dermatologic reactions including dermatitis, pruritus, dry skin, and acneiform during therapy; may occur ≥ 2 mo after therapy is complete. Treat as indicated with topical corticosteroids and topical and/or oral antibiotics. If Grade 2 dermatologic reaction occurs, if no improvement after 2 wk, ↓ amivantamab dose and continue lazertinib at same dose; reassess every 2 wk. If no improvement, ↓ lazertinib dose until reaction is Grade ≤1. If Grade 3 dermatologic reaction occurs, administer oral corticosteroids and hold lazertinib and amivantamab until recovery to Grade ≤2. Resume lazertinib at same or ↓ dose, resume amivantamab at ↓ dose. Permanently discontinue lazertinib and amivantamab if no improvement within 2 wk. If Grade 4 dermatologic reaction occurs, permanently discontinue amivantamab and hold lazertinib until recovery to Grade ≤2. Resume lazertinib at ↓ dose.
• Monitor for ocular toxicity such as keratitis or conjunctivitis during therapy. Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. If ocular toxicity confirmed,↓ lazertinib dose, or permanently discontinue amivantamab and continue lazertinib based on severity.

Lab Test Considerations:

• Verify negative pregnancy status before starting therapy.
• Screen for the presence of EGFR exon 19 deletions and exon 21 L858R substitution mutations in tumor specimens with an FDA-approved companion diagnostic test.