Active Ingredient: Amivantamab
Amivantamab is indicated in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with advanced NSCLC with activating EGFR Exon 20 insertion mutations.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Regimen A, in the case that patient weight is < 80 kg :
Intravenous, 1,400 milligrams amivantamab, once weekly, 4 doses in total, over the duration of 6 weeks. Afterwards, intravenous, 1,750 milligrams amivantamab, once weekly.
Regimen B, in the case that patient weight is ≥ 80 kg :
Intravenous, 1,750 milligrams amivantamab, once weekly, 4 doses in total, over the duration of 6 weeks. Afterwards, intravenous, 2,100 milligrams amivantamab, once every 3 weeks.
Premedications should be administered to reduce the risk of IRRs with amivantamab.
The recommended dosages of amivantamab, when used in combination with carboplatin and pemetrexed, is provided in the following table.
Recommended dosage of amivantamab every 3 weeks:
| Body weight at baselinea | Amivantamab dose | Schedule | Number of vials |
|---|---|---|---|
| Less than 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 | 4 |
| 1750 mg | Every 3 weeks starting at Week 7 onwards | 5 | |
| Greater than or equal to 80 kg | 1750 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 | 5 |
| 2100 mg | Every 3 weeks starting at Week 7 onwards | 6 |
a Dose adjustments not required for subsequent body weight changes.
When used in combination with carboplatin and pemetrexed, amivantamab should be administered after carboplatin and pemetrexed in the following order: pemetrexed, carboplatin and then amivantamab.
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 the table 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 3 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 | 1050 mg | 33 mL/hr | 50 mL/hr |
| Week 2 | 1400 mg | 65 mL/hr | |
| Week 3 | 1400 mg | 85 mL/hr | |
| Week 4 | 1400 mg | 125 mL/hr | |
| Subsequent weeks* | 1750 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 | 1400 mg | 25 mL/hr | 50 mL/hr |
| Week 2 | 1750 mg | 65 mL/hr | |
| Week 3 | 1750 mg | 85 mL/hr | |
| Week 4 | 1750 mg | 125 mL/hr | |
| Subsequent weeks* | 2100 mg | 125 mL/hr | |
* Starting at Week 7, patients are dosed every 3 weeks.
† Increase the initial infusion rate to the subsequent infusion rate after 2 hours in the absence of infusion-related reactions.
For:
Regimen A, in the case that patient weight is < 80 kg :
Subcutaneous, 1,600 milligrams amivantamab, one dose, over the duration of 1 week. Afterwards, subcutaneous, 2,400 milligrams amivantamab, once weekly, over the duration of 3 weeks. Afterwards, subcutaneous, 2,400 milligrams amivantamab, once every 3 weeks.
Regimen B, in the case that patient weight is ≥ 80 kg :
Subcutaneous, 2,240 milligrams amivantamab, one dose, over the duration of 1 week. Afterwards, subcutaneous, 3,360 milligrams amivantamab, once weekly, over the duration of 3 weeks. Afterwards, subcutaneous, 3,360 milligrams amivantamab, once every 3 weeks.
The recommended dosages of amivantamab subcutaneous formulation when used in combination with carboplatin and pemetrexed, based on baseline body weight, are provided in Table 1.
Table 1. Recommended dosage of amivantamab subcutaneous formulation in combination with carboplatin and pemetrexed (Every 3-week dosing):
| Body weight at baseline* | Recommended dose | Dosing schedule |
| Less than 80 kg | 1 600 mg | First dose at Week 1 Day 1 |
| 2 400 mg | • Weekly (total of 3 doses) from Weeks 2 to 4 • Every 3 weeks starting at Week 7 onwards | |
| Greater than or equal to 80 kg | 2 240 mg | First dose at Week 1 Day 1 |
| 3 360 mg | • Weekly (total of 3 doses) from Weeks 2 to 4 • Every 3 weeks starting at Week 7 onwards |
* Dose adjustments not required for subsequent body weight changes.
When used in combination with carboplatin and pemetrexed, amivantamab subcutaneous formulation should be administered after carboplatin and pemetrexed in the following order: pemetrexed, carboplatin and then amivantamab.
It is recommended that patients are treated with amivantamab subcutaneous formulation until disease progression or unacceptable toxicity.
Every 4-week or every 2-week dosing: If a dose of amivantamab subcutaneous formulation is missed between Weeks 1 to 4, it should be administered within 24 hours. If a dose of amivantamab subcutaneous formulation is missed from Week 5 onward, it should be administered within 7 days.
Every 3-week dosing: If a dose of amivantamab subcutaneous formulation is missed between Weeks 1 to 3, it should be administered within 24 hours. If a dose of amivantamab subcutaneous formulation is missed from Week 4 onward, it should be administered within 7 days.
If the missed dose is not administered according to this guidance, the missed dose should not be administered and the next dose should be administered per the usual dosing schedule.
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 Table 2. See also specific dose modifications for specific adverse reactions below Table 2.
Table 2. Recommended dose modifications for adverse reactions:
| Dose* | Dose after 1st interruption for adverse reaction | Dose after 2nd interruption for adverse reaction | Dose after 3rd interruption for adverse reaction |
| 1 600 mg | 1 050 mg | 700 mg | Discontinue amivantamab subcutaneous formulation |
| 2 240 mg | 1 600 mg | 1 050 mg | |
| 2 400 mg | 1 600 mg | 1 050 mg | |
| 3 360 mg | 2 240 mg | 1 600 mg | |
| 3 520 mg | 2 400 mg | 1 600 mg | |
| 4 640 mg | 3 360 mg | 2 240 mg |
* Dose at which the adverse reaction occurred
Premedications should be administered to reduce the risk of administration-related reactions with amivantamab subcutaneous formulation. Injections should be interrupted at the first sign of administration-related reactions. Additional supportive medicinal products (e.g., additional glucocorticoids, antihistamine, antipyretics and antiemetics) should be administered as clinically indicated.
Inject the required volume of amivantamab subcutaneous formulation into the subcutaneous tissue of the abdomen over approximately 5 minutes. Do not administer at other sites of the body as no data are available.
Pause or slow delivery rate if the patient experiences pain. In the event pain is not alleviated by pausing or slowing down delivery rate, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose.
If administering with a subcutaneous infusion set, ensure that the full dose is delivered through the infusion set. Sodium chloride 9 mg/mL (0.9%) solution may be utilised to flush remaining medicinal product through the line.
Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard, not intact or within 5 cm around the periumbilical area.
Injection sites should be rotated for successive injections.
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