AMIVANTAMAB-VMJW INJ,SOLN

Clinical Criteria Summary

Active or untreated brain metastases
Unable to tolerate pre-medications (acetaminophen + diphenhydramine + dexamethasone or methylprednisolone)
Pregnancy or lactating status

Locally advanced or metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 20 insertion mutation whose disease progressed on or after platinum-based chemotherapy
In combination with carboplatin and pemetrexed for first-line therapy of locally advanced or metastatic non-small cell lung cancer with EGFR exon 20 insertion mutation
In combination with Lazertinib for first-line therapy of locally advanced or metastatic non-small cell lung cancer with EGFR exon 19 deletion or exon 21 L858R substitution mutations (Give anticoagulant prophylaxis to prevent VTE during first 4 months of combination with lazertinib)
In combination with carboplatin and pemetrexed for locally advanced or metastatic non-small cell lung cancer with EGFR exon 19 deletion or exon 21 L858R substitution mutations in patients who progressed on or after an EGFR TKI

For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 3 months after stopping treatment
Screened for Hepatitis B and Hepatitis C and managed appropriately by provider as needed including a risk/benefit discussion
Care is provided by a VA/VA Community Care oncology provider
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Goals of care and role of Palliative Care consult have been discussed and documented

• Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)
• Must have epidermal growth factor receptor (EGFR) exon 20 insertion mutations
• Mutation must be detected by an FDA-approved test
• Disease must have progressed on or after platinum-based chemotherapy

• Weight-based dosing: Under 80 kg = 1050 mg; ≥80 kg = 1400 mg
• Dosing schedule: Weekly for 4 weeks (split Week 1 into 2 doses on Day 1 and Day 2), then every 2 weeks
• Infusion rates are weight- and week-dependent (e.g., Week 1 Day 1 initial rate 50 mL/hr, subsequent 75 mL/hr; Week 3+ up to 125 mL/hr)

• Acetaminophen 650 mg or 1000 mg prior to each dose
• Diphenhydramine 25-50 mg IV or oral prior to each dose
• Dexamethasone 10 mg or Methylprednisolone 40 mg required for initial doses (Week 1 Days 1 and 2); optional for subsequent doses

• Infusion-related reactions: Most common during Week 1 Day 1 and 2; premedication required; incidence lessens over time
• Interstitial Lung Disease/Pneumonitis: Monitor (incidence 3.3%, Grade 3-4 at 0.7%)
• Dermatologic Adverse Reactions: Rash/pruritus/dry skin in 74% (Grade 3 rash 3.3%); recommend avoiding sun exposure for 2 months, wearing protective clothing, and using UVA/UVB sunscreen daily
• Ocular toxicity: Monitor for keratitis, uveitis, dry eye, conjunctival redness, blurred vision, visual impairment (primarily Grades 1-2)
• Embryo-fetal toxicity warning present

• Contraindications: None stated
• Trial exclusions (clinical context): Untreated brain metastases; clinically significant cardiovascular disease; pregnancy/breastfeeding/planning pregnancy; positive Hepatitis B surface antigen or Hepatitis C antibody; HIV positive; clinically active liver disease; interstitial lung disease

• Second-line therapy for NSCLC following progression on first-line chemotherapy
• Alternative second-line options include mobocertinib; docetaxel is reserved for after progression on amivantamab or mobocertinib

• No important differences in efficacy or toxicity between patients ≥65 years old and younger patients