Rybrevant Injection Dosage

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

Medically reviewed by Drugs.com. Last updated on Sep 26, 2024.

Important Dosage Information

Administer premedications before each RYBREVANT infusion as recommended.
Administer diluted RYBREVANT intravenously according to the infusion rates in Tables 8 and 9, with the initial dose as a split infusion on Week 1 on Day 1 and Day 2.
Administer RYBREVANT via peripheral line for Week 1 Day 1 and 2 and Week 2 to reduce the risk of infusion-related reactions.
When administering RYBREVANT in combination with carboplatin and pemetrexed, infuse pemetrexed first, carboplatin second, and RYBREVANT last.
When administering RYBREVANT in combination with lazertinib, administer lazertinib orally any time before the RYBREVANT infusion.
When administering RYBREVANT in combination with lazertinib, administer anticoagulant prophylaxis to prevent venous thromboembolic (VTE) events for the first four months of treatment.

Patient Selection

Select patients for treatment with RYBREVANT based on the presence of a mutation as detected by an FDA-approved test.

Table 1: Patient Selection
Indication	Treatment Regimen	Source for Testing
Information on FDA approved tests is available at: http://www.fda.gov/CompanionDiagnostics.
First-Line Treatment of NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations	RYBREVANT in combination with lazertinib	Tumor or plasma specimens. Testing may be performed at any time from initial diagnosis. Testing does not need to be repeated once EGFR mutation status has been established.
Previously treated locally advanced or metastatic NSCLC with EGFR Exon 19 deletions or Exon 21 L858R substitution mutations (progressive disease on an EGFR tyrosine kinase inhibitor)	RYBREVANT in combination with carboplatin and pemetrexed
First-Line Treatment of NSCLC with EGFR Exon 20 Insertion Mutations	RYBREVANT in combination with carboplatin and pemetrexed
Previously Treated NSCLC with EGFR Exon 20 Insertion Mutations	RYBREVANT as a single agent

Recommended Dosage of RYBREVANT in Combination with Carboplatin and Pemetrexed for the treatment of NSCLC – Every 3-week dosing

The recommended dosage of RYBREVANT, administered in combination with carboplatin and pemetrexed is based on baseline body weight is provided in Table 2.

Table 2: Recommended Dosage for RYBREVANT in Combination with Carboplatin and Pemetrexed
Body weight at Baseline *	Recommended Dose	Dosing Schedule
* Dose adjustment is not required for subsequent body weight changes.
Less than 80 kg	1,400 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	1,750 mg	Every 3 weeks starting at Week 7 onwards
Greater than or equal to 80 kg	1,750 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
	2,100 mg	Every 3 weeks starting at Week 7 onwards

The recommended order of administration and regimen for RYBREVANT in combination with carboplatin and pemetrexed are provided in Table 3.

Table 3: Order of Administration and Regimen for RYBREVANT in Combination with Carboplatin and Pemetrexed
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 2 intravenously 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 2.	Every 3 weeks, continue until disease progression or unacceptable toxicity.

Recommended Dosage of RYBREVANT in Combination with Lazertinib or RYBREVANT as a Single Agent - Every 2-week dosing

The recommended dosage of RYBREVANT in combination with lazertinib or RYBREVANT as a single agent, based on baseline body weight, are provided in Table 4. Administer RYBREVANT until disease progression or unacceptable toxicity.

Table 4: Recommended Dosage Schedule for RYBREVANT in Combination with Lazertinib or RYBREVANT as a Single Agent
Body weight at Baseline *	Recommended Dose	Dosing Schedule
* Dose adjustment is not required for subsequent body weight changes.
Less than 80 kg	1,050 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	1,050 mg	Every 2 weeks starting at Week 7 onwards
Greater than or equal to 80 kg	1,400 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

RYBREVANT in Combination with Lazertinib

Order of Administration

When given in combination with lazertinib, administer RYBREVANT any time after lazertinib when given on the same day. Refer to the lazertinib prescribing information for recommended lazertinib dosing information. Administer RYBREVANT in combination with lazertinib until disease progression or unacceptable toxicity.

Concomitant Medications

When initiating treatment with RYBREVANT in combination with lazertinib, administer anticoagulant prophylaxis to prevent venous thromboembolic (VTE) events for the first four months of treatment. If there are no signs or symptoms of VTE during the first four months of treatment, consider discontinuation of anticoagulant prophylaxis at the discretion of the healthcare provider. Refer to the lazertinib prescribing information for information about concomitant medications.

When initiating treatment with RYBREVANT in combination with lazertinib, administer alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream and encourage patients to limit sun exposure during and for 2 months after treatment, to wear protective clothing and use broad-spectrum UVA/UVB sunscreen to reduce the risk of dermatologic adverse reactions. Consider prophylactic measures (e.g., use of oral antibiotics) to reduce the risk of dermatologic adverse reactions. Refer to the lazertinib prescribing information for information about concomitant medications.

Recommended Premedications

Prior to the initial infusion of RYBREVANT (Week 1, Day 1 and 2), administer premedications as described in Table 5 to reduce the risk of infusion-related reactions.

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 5) . Administer both antihistamine and antipyretic prior to all infusions.

Table 5: 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 6.

Table 6: Dose Reductions for Adverse Reactions for RYBREVANT
Dose at which the adverse reaction occurred	1 st Dose Reduction	2 nd Dose Reduction	3 rd Dose Reduction
1,050 mg	700 mg	350 mg	Discontinue RYBREVANT
1,400 mg	1,050 mg	700 mg
1,750 mg	1,400 mg	1,050 mg
2,100 mg	1,750 mg	1,400 mg

The recommended dosage modifications and management for adverse reactions for RYBREVANT are provided in Table 7.

Table 7: Recommended Dosage Modifications and Management for Adverse Reactions for RYBREVANT
Adverse Reaction	Severity	Dosage Modifications
Infusion-related reactions (IRR)	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 8 and 9). Include corticosteroid with premedications for subsequent dose (see Table 5).
	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 8 and 9). Include corticosteroid with premedications for subsequent dose (see Table 5). For recurrent Grade 3, permanently discontinue RYBREVANT.
	Grade 4	Permanently discontinue RYBREVANT.
Interstitial Lung Disease (ILD)/pneumonitis	Any Grade	Withhold RYBREVANT if ILD/pneumonitis is suspected. Permanently discontinue RYBREVANT if ILD/pneumonitis is confirmed.
Venous Thromboembolic (VTE) Events [Applies to the combination with lazertinib, see Warnings and Precautions (5.3)]	Grade 2 or 3	Withhold RYBREVANT and lazertinib. Administer anticoagulant treatment as clinically indicated. Once anticoagulant treatment has been initiated, resume RYBREVANT and lazertinib at the same dose level, at the discretion of the healthcare provider.
	Grade 4 or recurrent Grade 2 or 3 despite therapeutic level anticoagulation	Withhold lazertinib and permanently discontinue RYBREVANT. Administer anticoagulant treatment as clinically indicated. Once anticoagulant treatment has been initiated, treatment can continue with lazertinib at the same dose level at the discretion of the healthcare provider.
Dermatologic Adverse Reactions (including dermatitis acneiform, pruritus, dry skin)	Grade 1 or 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	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	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 Lazertinib

When administering RYBREVANT in combination with lazertinib, if there is an adverse reaction requiring dose reduction after withholding treatment and resolution, reduce the dose of RYBREVANT first.

Refer to the lazertinib prescribing information for information about dosage modifications for lazertinib.

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 7. 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 and number of RYBREVANT vials needed based on patient's baseline weight . Each vial of RYBREVANT contains 350 mg of amivantamab-vmjw.
Withdraw and then discard a volume of either 5% Dextrose Injection or 0.9% Sodium Chloride Injection 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 15°C to 25°C (59°F to 77°F).

Administration

Administer the diluted RYBREVANT solution 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, must be primed with either 5% Dextrose Injection or 0.9% Sodium Chloride Injection 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 until disease progression or unacceptable toxicity according to the infusion rates in Table 8.
Administer RYBREVANT via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related reactions during initial treatment.
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 8: Infusion Rates of RYBREVANT in Combination with Carboplatin and Pemetrexed for Treatment of NSCLC
* 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 is 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	1,050 mg	33	50
Week 2	1,400 mg	65
Week 3	1,400 mg	85
Week 4	1,400 mg	125
Weeks 5 and 6		No dose
Week 7 and every 3 weeks thereafter	1,750 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	1,400 mg	25	50
Week 2	1,750 mg	65
Week 3	1,750 mg	85
Week 4	1,750 mg	125
Week 5 and 6		No dose
Week 7 and every 3 weeks thereafter	2,100 mg	125

RYBREVANT in Combination with Lazertinib or RYBREVANT as a Single Agent

Administer RYBREVANT as a single agent infusion every 2 weeks intravenously until disease progression or unacceptable toxicity according to the infusion rates in Table 9.
Administer RYBREVANT via a peripheral line on Week 1 and Week 2, to reduce the risk of infusion-related reactions during initial treatment.
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.
When given in combination with lazertinib, administer RYBREVANT any time after lazertinib when given on the same day.

Table 9: Infusion Rates of RYBREVANT in Combination with Lazertinib or 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 is 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	1,050 mg	85
Week 3	1,050 mg	125
Week 4	1,050 mg	125
Week 5	1,050 mg	125
Week 6		No dose
Week 7 and every 2 weeks thereafter	1,050 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	1,050 mg	35	50
Week 2	1,400 mg	65
Week 3	1,400 mg	85
Week 4	1,400 mg	125
Week 5	1,400 mg	125
Week 6		No dose
Week 7 and every 2 weeks thereafter	1,400 mg	125