Rybrevant Injection Dosage

Generic name: AMIVANTAMAB 350mg
Dosage form: injection
Drug class: Miscellaneous antineoplastics

Medically reviewed by Drugs.com. Last updated on Mar 8, 2024.

Important Dosage Information

Administer premedications before each RYBREVANT infusion as recommended [see Dosage and Administration (2.5)].
Administer diluted RYBREVANT intravenously according to the infusion rates in Tables 7 and 8, with the initial dose as a split infusion on Week 1 on Day 1 and Day 2 [see Dosage and Administration (2.8)].
Administer RYBREVANT via peripheral line for Week 1 Day 1 and 2 and Week 2 to reduce the risk of infusion-related reactions [see Dosage and Administration 2.8].
When administering RYBREVANT in combination with carboplatin and pemetrexed, infuse pemetrexed first, carboplatin second, and RYBREVANT last [see Dosage and Administration 2.8].

Patient Selection

Select patients for treatment with RYBREVANT based on the presence of EGFR exon 20 insertion mutations in tumor or plasma specimens [see Clinical Studies (14)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage of RYBREVANT for First-line Treatment of NSCLC with Exon 20 Insertion Mutations (RYBREVANT in Combination with Carboplatin and Pemetrexed)

The recommended dosages of RYBREVANT, administered in combination with carboplatin and pemetrexed, based on baseline body weight are provided in Table 1.

Table 1: Recommended Dosage for RYBREVANT in Combination with Carboplatin and Pemetrexed
Body weight at Baseline *	Recommended Dose	Dosing Schedule
* Dose adjustments not required for subsequent body weight changes.
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 Weeks 5 and 6 – no dose
Less than 80 kg	1750 mg	Every 3 weeks starting at Week 7 onwards
Greater than or equal to 80 kg	1750 mg	Weekly (total of 4 doses) for Weeks 1 to 4 Week 1 - split infusion on Day 1 and Day 2 Weeks 2 to 4 - infusion on Day 1 Weeks 5 and 6 – no dose
	2100 mg	Every 3 weeks starting at Week 7 onwards

The recommended order of administration and regimen for RYBREVANT in combination with carboplatin and pemetrexed is provided in Table 2.

Table 2: Order of Administration and Regimen for RYBREVANT in Combination with Pemetrexed and Carboplatin
RYBREVANT in Combination with Carboplatin and Pemetrexed
Administer the regimen in the following order: pemetrexed first, carboplatin second and RYBREVANT last.
Drug	Dose	Duration/Timing of Treatment
Pemetrexed	Pemetrexed 500 mg/m 2intravenously Refer to the pemetrexed Full Prescribing Information for complete information.	Every 3 weeks, continue until disease progression or unacceptable toxicity.
Carboplatin	Carboplatin AUC 5 intravenously Refer to the carboplatin Full Prescribing Information for complete information.	Every 3 weeks for up to 12 weeks.
RYBREVANT	RYBREVANT intravenously See Table 1.	Every 3 weeks, continue until disease progression or unacceptable toxicity.

Recommended Dosage of RYBREVANT for Patients with Previously Treated NSCLC with Exon 20 Insertion Mutations (RYBREVANT as a Single Agent)

The recommended dosages of RYBREVANT as a single agent, based on baseline body weight, are provided in Table 3.

Table 3: Recommended Dosage Schedule for RYBREVANT as a Single Agent
Body weight at Baseline *	Recommended Dose	Dosing Schedule
* Dose adjustments not required for subsequent body weight changes.
Less than 80 kg	1050 mg	Weekly (total of 5 doses) from Weeks 1 to 5 Week 1 - split infusion on Day 1 and Day 2 Weeks 2 to 5 - infusion on Day 1 Week 6 – no dose
Less than 80 kg	1050 mg	Every 2 weeks starting at Week 7 onwards
Greater than or equal to 80 kg	1400 mg	Weekly (total of 5 doses) from Weeks 1 to 5 Week 1 - split infusion on Day 1 and Day 2 Weeks 2 to 5 - infusion on Day 1 Week 6 – no dose
		Every 2 weeks starting at Week 7 onwards

Administer RYBREVANT until disease progression or unacceptable toxicity.

Recommended Premedications

Prior to the initial infusion of RYBREVANT (Week 1, Day 1 and 2), administer premedication as described in Table 4 to reduce the risk of infusion-related reactions [see Warnings and Precautions (5.1)].

Glucocorticoid administration is required for Week 1, Day 1 and 2 dose only and upon re-initiation after prolonged dose interruptions, then as necessary for subsequent infusions (see Table 4). Administer both antihistamine and antipyretic prior to all infusions.

Table 4: Premedications
Medication	Dose	Route of Administration	Dosing Window Prior to RYBREVANT Administration
* Required at all doses. † Required at initial dose (Week 1 Day 1) ‡ Required at second dose (Week 1 Day 2); optional for subsequent doses.
Antihistamine *	Diphenhydramine (25 to 50 mg) or equivalent	Intravenous	15 to 30 minutes
Antihistamine *	Diphenhydramine (25 to 50 mg) or equivalent	Oral	30 to 60 minutes
Antipyretic *	Acetaminophen (650 to 1,000 mg)	Intravenous	15 to 30 minutes
Antipyretic *	Acetaminophen (650 to 1,000 mg)	Oral	30 to 60 minutes
Glucocorticoid †	Dexamethasone (20 mg) or equivalent	Intravenous	45 to 60 minutes
Glucocorticoid ‡	Dexamethasone (10 mg) or equivalent	Intravenous	45 to 60 minutes

Dosage Modifications for Adverse Reactions

The recommended dose reductions for adverse reactions for RYBREVANT are listed in Table 5.

Table 5: Dose Reductions for Adverse Reactions for RYBREVANT
Dose *	1 stDose Reduction	2 ndDose Reduction	3 rdDose Reduction
* Dose at which the adverse reaction occurred
1050 mg	700 mg	350 mg	Discontinue RYBREVANT
1400 mg	1050 mg	700 mg
1750 mg	1400 mg	1050 mg
2100 mg	1750 mg	1400 mg

The recommended dosage modifications and management for adverse reactions for RYBREVANT are provided in Table 6.

Table 6: Recommended Dosage Modifications and Management for Adverse Reactions for RYBREVANT
Adverse Reaction	Severity	Dosage Modifications
Infusion-related reactions (IRR) [see Warnings and Precautions (5.1)]	Grade 1 to 2	Interrupt RYBREVANT infusion if IRR is suspected and monitor patient until reaction symptoms resolve. Resume the infusion at 50% of the infusion rate at which the reaction occurred. If there are no additional symptoms after 30 minutes, the infusion rate may be escalated (see Tables 7and 8). Include corticosteroid with premedications for subsequent dose (see Table 4).
	Grade 3	Interrupt RYBREVANT infusion and administer supportive care medications. Continuously monitor patient until reaction symptoms resolve. Resume the infusion at 50% of the infusion rate at which the reaction occurred. If there are no additional symptoms after 30 minutes, the infusion rate may be escalated (see Tables 7and 8). Include corticosteroid with premedications for subsequent dose (see Table 4). For recurrent Grade 3, permanently discontinue RYBREVANT.
	Grade 4	Permanently discontinue RYBREVANT.
Interstitial Lung Disease (ILD)/pneumonitis [see Warnings and Precautions (5.2)]	Any Grade	Withhold RYBREVANT if ILD/pneumonitis is suspected. Permanently discontinue RYBREVANT if ILD/pneumonitis is confirmed.
Dermatologic Adverse Reactions (including dermatitis acneiform, pruritus, dry skin) [see Warnings and Precautions (5.3)]	Grade 1	Initiate supportive care management. Reassess after 2 weeks.
	Grade 2	Initiate supportive care management. Reassess after 2 weeks; if rash does not improve, consider dose reduction.
	Grade 3	Withhold RYBREVANT and initiate supportive care management. Upon recovery to ≤ Grade 2, resume RYBREVANT at reduced dose. If no improvement within 2 weeks, permanently discontinue treatment.
	Grade 4	Permanently discontinue RYBREVANT.
	Severe bullous, blistering or exfoliating skin conditions (including toxic epidermal necrolysis (TEN)	Permanently discontinue RYBREVANT.
Other Adverse Reactions [see Adverse Reactions (6.1)]	Grade 3	Withhold RYBREVANT until recovery to ≤ Grade 1 or baseline. Resume at the same dose if recovery occurs within 1 week. Resume at reduced dose if recovery occurs after 1 week but within 4 weeks. Permanently discontinue if recovery does not occur within 4 weeks.
Other Adverse Reactions [see Adverse Reactions (6.1)]	Grade 4	Withhold RYBREVANT until recovery to ≤Grade 1 or baseline. Resume at reduced dose if recovery occurs within 4 weeks. Permanently discontinue if recovery does not occur within 4 weeks. Permanently discontinue for recurrent Grade 4 reactions.

Recommended Dosage Modifications for Adverse Reactions for RYBREVANT in Combination with Carboplatin and Pemetrexed

When administering RYBREVANT in combination with carboplatin and pemetrexed, modify the dosage of one or more drugs. Withhold or discontinue RYBREVANT as shown in Table 6. Refer to prescribing information for carboplatin and pemetrexed for additional dosage modification information.

Preparation

Dilute and prepare RYBREVANT for intravenous infusion before administration.

Check that the RYBREVANT solution is colorless to pale yellow. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if discoloration or visible particles are present.
Determine the dose required of RYBREVANT needed based on patient's baseline weight [see Dosage and Administration (2.3)] . Each vial of RYBREVANT contains 350 mg of amivantamab-vmjw.
Withdraw and then discard a volume of either 5% dextrose solution or 0.9% sodium chloride solution from the 250 mL infusion bag equal to the volume of RYBREVANT to be added (i.e., discard 7 mL diluent from the infusion bag for each RYBREVANT vial). Only use infusion bags made of polyvinylchloride (PVC), polypropylene (PP), polyethylene (PE), or polyolefin blend (PP+PE).
Withdraw 7 mL of RYBREVANT from each vial and add it to the infusion bag. The final volume in the infusion bag should be 250 mL. Discard any unused portion left in the vial.
Gently invert the bag to mix the solution. Do not shake.
Diluted solutions should be administered within 10 hours (including infusion time) at room temperature 59°F to 77°F (15°C to 25°C).

Administration

Administer the diluted RYBREVANT solution [see Dosage and Administration (2.7)] by intravenous infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.2 micrometer).
Administration sets must be made of either polyurethane (PU), polybutadiene (PBD), PVC, PP, or PE.
The administration set with filter, mustbe primed with either 5% dextrose solution or 0.9% sodium chloride solution prior to the initiation of each RYBREVANT infusion.
Do not infuse RYBREVANT concomitantly in the same intravenous line with other agents.

RYBREVANT in Combination with Carboplatin and Pemetrexed

Administer RYBREVANT in combination with carboplatin and pemetrexed infusions every 3 weeks intravenously according to the infusion rates in Table 7.
Administer RYBREVANT via a peripheral line on Week 1 and Week 2 given the high incidence of infusion-related reactions during initial treatment [see Warnings and Precautions (5.1)].
RYBREVANT may be administered via central line for subsequent weeks.
For the initial infusion, prepare RYBREVANT as close to administration time as possible to allow for the possibility of extended infusion time in the event of an infusion related reaction.
Administer the pemetrexed infusion first, carboplatin infusion second, and the RYBREVANT infusion last.

Table 7: Infusion Rates of RYBREVANT for First-line Treatment of NSCLC with Exon 20 Insertion Mutations (RYBREVANT in Combination with Carboplatin and Pemetrexed)
* In the absence of infusion-related reactions, increase the initial infusion rate to the subsequent infusion rate after 2 hours based on patient tolerance. Total infusion time approximately 4–6 hours for day 1 and 6–8 hours for day 2. Subsequent infusion time is approximately 2 hours.
Body Weight Less Than 80 kg
Week	Dose (per 250 mL bag)	Initial Infusion Rate (mL/hr)	Subsequent Infusion Rate* (mL/hr)
Week 1 (split dose infusion)
Week 1 Day 1	350 mg	50	75
Week 1 Day 2	1050 mg	33	50
Week 2	1400 mg	65
Week 3	1400 mg	85
Week 4	1400 mg	125
Weeks 5 and 6		No dose
Week 7 and every 3 weeks thereafter	1750 mg	125
Body Weight Greater Than or Equal to 80 kg
Week	Dose (per 250 mL bag)	Initial Infusion Rate (mL/hr)	Subsequent Infusion Rate (mL/hr)
Week 1 (split dose infusion)
Week 1 Day 1	350 mg	50	75
Week 1 Day 2	1400 mg	25	50
Week 2	1750 mg	65
Week 3	1750 mg	85
Week 4	1750 mg	125
Week 5 and 6		No dose
Week 7 and every 3 weeks thereafter	2100 mg	125

RYBREVANT as a Single Agent

Administer RYBREVANT as a single agent infusion every 2 weeks intravenously according to the infusion rates in Table 8.
Administer RYBREVANT via a peripheral line on Week 1 and Week 2, given the high incidence of infusion-related reactions during initial treatment [see Warnings and Precautions (5.1)].
RYBREVANT may be administered via central line for subsequent weeks.
For the initial infusion, prepare RYBREVANT as close to administration time as possible to allow for the possibility of extended infusion time in the event of an infusion related reaction.

Table 8: Infusion Rates of RYBREVANT for Patients with Previously Treated NSCLC with Exon 20 Insertion Mutations (RYBREVANT as Single Agent)
* In the absence of infusion-related reactions, increase the initial infusion rate to the subsequent infusion rate after 2 hours based on patient tolerance. Total infusion time approximately 4–6 hours for day 1 and 6–8 hours for day 2. Subsequent infusion time is approximately 2 hours.
Body Weight Less Than 80 kg
Week	Dose (per 250 mL bag)	Initial Infusion Rate (mL/hr)	Subsequent Infusion Rate* (mL/hr)
Week 1 (split dose infusion)
Week 1 Day 1	350 mg	50	75
Week 1 Day 2	700 mg	50	75
Week 2	1050 mg	85
Week 3	1050 mg	125
Week 4	1050 mg	125
Week 5	1050 mg	125
Week 6		No dose
Week 7 and every 2 weeks thereafter	1050 mg	125
Body Weight Greater Than or Equal to 80 kg
Week	Dose (per 250 mL bag)	Initial Infusion Rate (mL/hr)	Subsequent Infusion Rate * (mL/hr)
Week 1 (split dose infusion)
Week 1 Day 1	350 mg	50	75
Week 1 Day 2	1050 mg	35	50
Week 2	1400 mg	65
Week 3	1400 mg	85
Week 4	1400 mg	125
Week 5	1400 mg	125
Week 6		No dose
Week 7 and every 2 weeks thereafter	1400 mg	125