Active Ingredient: Amivantamab
Amivantamab is indicated as monotherapy for treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) Exon 20 insertion mutations, after failure of platinum-based therapy.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Regimen A: In case that patient weight is ≤ 80 kg, intravenous, 1,050 milligrams amivantamab, once weekly, over the duration of 4 weeks. Afterwards, in case that patient weight is ≤ 80 kg, intravenous, 1,050 milligrams amivantamab, once every 2 weeks.
Regimen B: In case that patient weight is ≥ 80 kg, intravenous, 1,400 milligrams amivantamab, once weekly, over the duration of 4 weeks. Afterwards, in case that patient weight is ≥ 80 kg, intravenous, 1,400 milligrams amivantamab, once every 2 weeks.
Premedications should be administered to reduce the risk of IRRs with amivantamab.
The recommended dosages of amivantamab monotherapy is provided in the following table.
Recommended dosage of amivantamab every 2 weeks:
| Body weight at baselinea | Amivantamab dose | Schedule |
|---|---|---|
| Less than 80 kg | 1050 mg | Weekly (total of 4 doses) from weeks 1 to 4 • Week 1 – split infusion on Day 1 and Day 2 • Weeks 2 to 4 – infusion on Day 1 |
| Every 2 weeks starting at Week 5 onwards | ||
| Greater than or equal to 80 kg | 1400 mg | Weekly (total of 4 doses) from Weeks 1 to 4 • Week 1 – split infusion on Day 1 and Day 2 • Weeks 2 to 4 – infusion on Day 1 |
| Every 2 weeks starting at Week 5 onwards |
a Dose adjustments not required for subsequent body weight changes.
It is recommended that patients are treated with amivantamab until disease progression or unacceptable toxicity.
If a planned dose is missed, the dose should be administered as soon as possible and the dosing schedule should be adjusted accordingly, maintaining the treatment interval.
Dosing should be interrupted for Grade 3 or 4 adverse reactions until the adverse reaction resolves to ≤ Grade 1 or baseline. If an interruption is 7 days or less, restart at the current dose. If an interruption is longer than 7 days, it is recommended restarting at a reduced dose as presented in the following table.
Recommended dose modifications for adverse reactions:
| Dose at which the adverse reaction occurred | Dose after 1st interruption for adverse reaction | Dose after 2nd interruption for adverse reaction | Dose after 3rd interruption for adverse reaction |
|---|---|---|---|
| 1050 mg | 700 mg | 350 mg | Discontinue amivantamab |
| 1400 mg | 1050 mg | 700 mg | |
| 1750 mg | 1400 mg | 1050 mg | |
| 2100 mg | 1750 mg | 1400 mg |
Prior to infusion (Week 1, Days 1 and 2), antihistamines, antipyretics, and glucocorticoids should be administered to reduce the risk of IRRs. For subsequent doses, antihistamines and antipyretics are required to be administered. Glucocorticoids should also be re-initiated after prolonged dose interruptions. Antiemetics should be administered as needed.
Dosing schedule of premedications:
| Premedication | Dose | Route of administration | Recommended dosing window prior to amivantamab administration |
|---|---|---|---|
| Antihistamine* | Diphenhydramine (25 to 50 mg) or equivalent | Intravenous | 15 to 30 minutes |
| Oral | 30 to 60 minutes | ||
| Antipyretic* | Paracetamol/Acetaminophen (650 to 1000 mg) | Intravenous | 15 to 30 minutes |
| Oral | 30 to 60 minutes | ||
| Glucocorticoid‡ | Dexamethasone (20 mg) or equivalent | Intravenous | 60 to 120 minutes |
| Glucocorticoid+ | Dexamethasone (10 mg) or equivalent | Intravenous | 45 to 60 minutes |
* Required at all doses.
‡ Required at initial dose (Week 1, Day 1) or at the next subsequent dose in the event of an IRR.
+ Required at second dose (Week 1, Day 2); optional for subsequent doses.
The infusion should be administered intravenously at the infusion rates presented in Table 5 or 6 below. Due to the frequency of IRRs at the first dose, amivantamab should be infused via a peripheral vein at Week 1 and Week 2; infusion via a central line may be administered for subsequent weeks when the risk of IRR is lower. It is recommended for the first dose to be prepared as close to administration as possible to maximise the likelihood of completing the infusion in the event of an IRR.
Infusion rates for amivantamab every 2 weeks:
| Body weight less than 80 kg | |||
| Week | Dose (per 250 mL bag) | Initial infusion rate | Subsequent infusion rate‡ |
| Week 1 (split dose infusion) | |||
| Week 1 Day 1 | 350 mg | 50 mL/hr | 75 mL/hr |
| Week 1 Day 2 | 700 mg | 50 mL/hr | 75 mL/hr |
| Week 2 | 1050 mg | 85 mL/hr | |
| Subsequent weeks* | 1050 mg | 125 mL/hr | |
| Body weight greater than or equal to 80 kg | |||
| Week | Dose (per 250 mL bag) | Initial infusion rate | Subsequent infusion rate‡ |
| Week 1 (split dose infusion) | |||
| Week 1 Day 1 | 350 mg | 50 mL/hr | 75 mL/hr |
| Week 1 Day 2 | 1050 mg | 35 mL/hr | 50 mL/hr |
| Week 2 | 1400 mg | 65 mL/hr | |
| Week 3 | 1400 mg | 85 mL/hr | |
| Subsequent weeks* | 1400 mg | 125 mL/hr | |
* After Week 5, patients are dosed every 2 weeks.
‡ Increase the initial infusion rate to the subsequent infusion rate after 2 hours in the absence of IRRs
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