Rybrevant

RYBREVANT- amivantamab injection
Janssen Biotech, Inc.

1 INDICATIONS AND USAGE

RYBREVANT is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1)] , whose disease has progressed on or after platinum-based chemotherapy.

This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

2 DOSAGE AND ADMINISTRATION

2.1 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.

2.2 Recommended Dosage

​ The recommended doses of RYBREVANT, based on baseline body weight, are provided in Table 1, and the dosing schedule is provided in Table 2.

Table 1: Recommended Dose of RYBREVANT Based on Baseline Body Weight

Body Weight at Baseline *	Recommended Dose	Number of 350 mg/7 mL RYBREVANT Vials
* Dose adjustments not required for subsequent body weight changes.
Less than 80 kg	1050 mg	3
Greater than or equal to 80 kg	1400 mg	4

Table 2: Dosing schedule for RYBREVANT

​ Weeks	Schedule
Weeks 1 to 4	Weekly (total of 4 doses)
​	Week 1 — split infusion on Day 1 and Day 2
​	Weeks 2 to 4 — infusion on Day 1
​ Week 5 onwards	Every 2 weeks starting at Week 5

​ Administer premedications before each RYBREVANT infusion as recommended [see Dosage and Administration (2.3)]. Administer diluted RYBREVANT intravenously according to the infusion rates in Table 6, with the initial dose as a split infusion on Week 1 on Day 1 and Day 2 [see Dosage and Administration (2.5), (2.6)]. Administer RYBREVANT until disease progression or unacceptable toxicity.

2.3 Recommended Premedications

Prior to initial infusion of RYBREVANT (Week 1, Days 1 and 2), administer premedication as described in Table 3 to reduce the risk of infusion-related reactions: [see Warnings and Precautions (5.1)]

Table 3: Premedications

Medication	Dose	Route of Administration	Dosing Window Prior to RYBREVANT Administration
* Required at all doses. † Required at initial dose (Week 1, Days 1 and 2); optional for subsequent doses.
Antihistamine *	Diphenhydramine (25 to 50 mg) or equivalent	Intravenous	15 to 30 minutes
		Oral	30 to 60 minutes
Antipyretic *	Acetaminophen (650 to 1,000 mg)	Intravenous	15 to 30 minutes
		Oral	30 to 60 minutes
Glucocorticoid †	Dexamethasone (10 mg) or Methylprednisolone (40 mg) or equivalent	Intravenous	45 to 60 minutes

Administer both antihistamine and antipyretic prior to all infusions. Glucocorticoid administration required for Week 1, Days 1 and 2 doses only and as necessary for subsequent infusions.

2.4 Dosage Modifications for Adverse Reactions

The recommended RYBREVANT dose reductions for adverse reactions (see Table 5) are listed in Table 4.

Table 4: RYBREVANT Dose Reductions for Adverse Reactions

Body Weight at Baseline	Initial Dose	1st Dose Reduction	2nd Dose Reduction	3rd Dose Reduction
Less than 80 kg	1050 mg	700 mg	350 mg	Discontinue RYBREVANT
Greater than or equal to 80 kg	1400 mg	1050 mg	700 mg

The recommended RYBREVANT dosage modifications for adverse reactions are provided in Table 5.

Table 5: Recommended RYBREVANT Dosage Modifications for Adverse Reactions

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 Table 6). Include corticosteroid with premedications for subsequent dose (see Table 3).
	Grade 3	Interrupt RYBREVANT infusion and administer supportive care medications. 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 Table 6). Include corticosteroid with premedications for subsequent dose (see Table 3). 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 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.
	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.