Amivantamab

EVERY-3-WEEKS SCHEDULE (in combination with carboplatin and pemetrexed, SPC Table 1): baseline weight less than 80 kg — 1400 mg weekly for a total of 4 doses from Weeks 1 to 4 (Week 1 split over Day 1 and Day 2), then 1750 mg every 3 weeks from Week 7 onwards; baseline weight 80 kg or more — 1750 mg weekly for 4 doses from Weeks 1 to 4 (Week 1 split), then 2100 mg every 3 weeks from Week 7 onwards. Dose adjustments are NOT required for subsequent body weight changes. Give amivantamab AFTER carboplatin and pemetrexed, in the order pemetrexed, carboplatin, then amivantamab. When given with lazertinib on the same day, administer amivantamab any time after lazertinib. EGFR mutation status must be established with a validated test before starting, and treatment initiated and supervised by a physician experienced in anticancer medicinal products, with access to support for infusion-related reactions. PREMEDICATION (SPC Table 4): two days before the first infusion give dexamethasone 8 mg orally twice daily; on the day of the initial infusion (Week 1 Day 1) give dexamethasone 8 mg orally 60 minutes before, plus intravenous dexamethasone 20 mg or equivalent 60 to 120 minutes before; antihistamine (chlorphenamine 10 mg intravenously or equivalent) 15 to 30 minutes before and antipyretic (paracetamol 650 to 1000 mg) 15 to 30 minutes before if intravenous or 30 to 60 minutes before if oral — antihistamine and antipyretic are required at ALL doses; intravenous dexamethasone 10 mg or equivalent 45 to 60 minutes before is required at the second dose (Week 1 Day 2) and optional for subsequent doses. Glucocorticoids should be re-initiated after prolonged dose interruptions and antiemetics given as needed. VTE PROPHYLAXIS: when used with lazertinib, prophylactic anticoagulation (for example low-molecular-weight heparin) is recommended for the first four months; vitamin K antagonists are not recommended. Patients should limit sun exposure during and for 2 months after therapy. DOSE MODIFICATIONS (SPC Table 3 — interrupt for Grade 3 or 4 reactions until resolution to Grade 1 or less or baseline; restart at the current dose if the interruption is 7 days or less, at a reduced dose if longer): 1050 mg to 700 mg to 350 mg then discontinue; 1400 mg to 1050 mg to 700 mg; 1750 mg to 1400 mg to 1050 mg; 2100 mg to 1750 mg to 1400 mg. INFUSION-RELATED REACTIONS: interrupt at the first sign; for Grade 1 to 3, resume at 50% of the previous rate on recovery and give dexamethasone 20 mg or equivalent with the next dose; permanently discontinue for recurrent Grade 3 or Grade 4. ILD: withhold if interstitial lung disease or pneumonitis is suspected and permanently discontinue if confirmed. INFUSION RATES (mL/hr per 250 mL bag; increase from the initial to the subsequent rate after 2 hours in the absence of infusion-related reactions) — EVERY 2 WEEKS, less than 80 kg: Week 1 Day 1 350 mg at 50 then 75 mL/hr, Week 1 Day 2 700 mg at 50 then 75 mL/hr, Week 2 1050 mg at 85 mL/hr, subsequent weeks 1050 mg at 125 mL/hr; 80 kg or more: Week 1 Day 1 350 mg at 50 then 75 mL/hr, Week 1 Day 2 1050 mg at 35 then 50 mL/hr, Week 2 1400 mg at 65 mL/hr, Week 3 1400 mg at 85 mL/hr, subsequent weeks 1400 mg at 125 mL/hr. EVERY 3 WEEKS, less than 80 kg: Week 1 Day 1 350 mg at 50 then 75 mL/hr, Week 1 Day 2 1050 mg at 33 then 50 mL/hr, Week 2 1400 mg at 65 mL/hr, Week 3 1400 mg at 85 mL/hr, Week 4 1400 mg at 125 mL/hr, subsequent weeks 1750 mg at 125 mL/hr; 80 kg or more: Week 1 Day 1 350 mg at 50 then 75 mL/hr, Week 1 Day 2 1400 mg at 25 then 50 mL/hr, Week 2 1750 mg at 65 mL/hr, Week 3 1750 mg at 85 mL/hr, Week 4 1750 mg at 125 mL/hr, subsequent weeks 2100 mg at 125 mL/hr. MISSED DOSE: administer as soon as possible and adjust the schedule, maintaining the treatment interval. ELDERLY: no dose adjustment necessary. HEPATIC: no adjustment for mild impairment; caution in moderate or severe impairment (not studied). PAEDIATRIC: there is no relevant use of amivantamab in the paediatric population in non-small cell lung cancer. NOTE: this draft is based on the eMC SPC for Rybrevant 350 mg concentrate for solution for infusion (intravenous); it does NOT cover any subcutaneous amivantamab product.