Rybrevant Faspro

Dosage and Administration ( 2.1 ) 02/2026 Dosage and Administration ( 2.3 ) 02/2026 Dosage and Administration ( 2.7 ) 02/2026 Dosage and Administration ( 2.8 ) 02/2026 Dosage and Administration ( 2.9 ) 02/2026

1 INDICATIONS AND USAGE RYBREVANT FASPRO is a combination of amivantamab, a bispecific EGF receptor-directed and MET receptor-directed antibody, and hyaluronidase, an endoglycosidase indicated: in combination with lazertinib for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test. ( 1 , 2.2 ) in combination with carboplatin and pemetrexed for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor. ( 1 , 2.2 ) in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. ( 1 , 2.2 ) as a single agent for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. ( 1 , 2.2 ) 1.1 First-Line Treatment of NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations RYBREVANT FASPRO, in combination with lazertinib, is indicated for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test [see Dosage and Administration (2.2) ] . 1.2 Previously Treated NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations RYBREVANT FASPRO, in combination with carboplatin and pemetrexed, is indicated for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor [see Dosage and Administration (2.2) ]. 1.3 First-Line Treatment of NSCLC with EGFR Exon 20 Insertion Mutations RYBREVANT FASPRO, in combination with carboplatin and pemetrexed, is indicated for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test [see Dosage and Administration (2.2) ] . 1.4 Previously Treated NSCLC with EGFR Exon 20 Insertion Mutations RYBREVANT FASPRO is indicated as a single agent for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test [see Dosage and Administration (2.2) ] , whose disease has progressed on or after platinum-based chemotherapy.

2 DOSAGE AND ADMINISTRATION For subcutaneous use only. (2.1) RYBREVANT FASPRO has different recommended dosage and administration than intravenous amivantamab products. ( 2.1 ) Administer each injection of RYBREVANT FASPRO subcutaneously in the abdomen over approximately 5 minutes. ( 2.1 ) The recommended dosage of RYBREVANT FASPRO is based on baseline body weight. ( 2.3 ) Administer premedications as recommended. ( 2.4 ) Recommended dosage for RYBREVANT FASPRO in combination with carboplatin and pemetrexed (every 3-week dosing), see Table 2 . ( 2.3 ) Recommended dosage for RYBREVANT FASPRO in combination with lazertinib or for RYBREVANT FASPRO as a single agent (every 4-week dosing), see Table 4 . ( 2.3 ) Recommended dosage for RYBREVANT FASPRO in combination with lazertinib or for RYBREVANT FASPRO as a single agent (every 2-week dosing), see Table 5 . ( 2.3 ) 2.1 Important Dosage and Administration Information RYBREVANT FASPRO is for subcutaneous use only. Do not administer RYBREVANT FASPRO intravenously. RYBREVANT FASPRO must be administered by a healthcare professional. To reduce the risk of medication errors, prior to administration, check the vial labels to ensure that the drug being prepared and administered is subcutaneous RYBREVANT FASPRO and not intravenous amivantamab. RYBREVANT FASPRO has different recommended dosage and administration than intravenous amivantamab products. Do not substitute RYBREVANT FASPRO for or with intravenous amivantamab products. Adult patients currently receiving intravenous amivantamab at an every 2-week dosing regimen may switch to subcutaneous RYBREVANT FASPRO at an every 2-week dosing regimen or at an every 4-week dosing regimen at their next scheduled dose on or after Week 5. Adult patients currently receiving intravenous amivantamab at an every 3-week dosing regimen may switch to subcutaneous RYBREVANT FASPRO at an every 3-week dosing regimen at their next scheduled dose on or after Week 4. Adult patients currently receiving RYBREVANT FASPRO at an every 2-week dosing regimen may switch to an every 4-week dosing regimen at their next scheduled dose on or after Week 5. RYBREVANT FASPRO is not indicated for use in pediatric patients. Administer premedications before each RYBREVANT FASPRO dose as recommended, to reduce the risk of administration-related reactions (ARRs) [see Dosage and Administration (2.4) ] . Administer each injection of RYBREVANT FASPRO subcutaneously in the abdomen over approximately 5 minutes to minimize injection site irritation. Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard, not intact or within 2 inches (5 cm) around the periumbilical area. If the total dose requires multiple injections of RYBREVANT FASPRO, administer each injection consecutively in separate quadrants of the abdomen, with each injection taking approximately 5 minutes. Rotate injection sites at the next scheduled dose. Pause or slow the 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, 0.9% sodium chloride solution may be utilized to flush remaining drug product through the line. Discard unused portion. 2.2 Patient Selection Select patients for treatment with RYBREVANT FASPRO based on the presence of a mutation as detected by an FDA-approved test as shown in Table 1. 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 [see Indications and Usage (1.1) ] RYBREVANT FASPRO in combination with lazertinib Tumor or plasma specimens. Testing may be performed …

3 DOSAGE FORMS AND STRENGTHS Injection 1,600 mg amivantamab and 20,000 units hyaluronidase per 10 mL (160 mg and 2,000 units/mL) clear to opalescent and colorless to pale yellow solution in a single-dose vial. 2,240 mg amivantamab and 28,000 units hyaluronidase per 14 mL (160 mg and 2,000 units/mL) clear to opalescent and colorless to pale yellow solution in a single-dose vial. 2,400 mg amivantamab and 30,000 units hyaluronidase per 15 mL (160 mg and 2,000 units/mL) clear to opalescent and colorless to pale yellow solution in a single-dose vial. 3,520 mg amivantamab and 44,000 units hyaluronidase per 22 mL (160 mg and 2,000 units/mL) clear to opalescent and colorless to pale yellow solution in a single-dose vial. Injection : 1,600 mg amivantamab and 20,000 units hyaluronidase per 10 mL (160 mg and 2,000 units/mL) solution in a single-dose vial. ( 3 ) 2,240 mg amivantamab and 28,000 units hyaluronidase per 14 mL (160 mg and 2,000 units/mL) solution in a single-dose vial. ( 3 ) 2,400 mg amivantamab and 30,000 units hyaluronidase per 15 mL (160 mg and 2,000 units/mL) solution in a single-dose vial. ( 3 ) 3,520 mg amivantamab and 44,000 units hyaluronidase per 22 mL (160 mg and 2,000 units/mL) solution in a single-dose vial. ( 3 )

4 CONTRAINDICATIONS RYBREVANT FASPRO is contraindicated in patients with known hypersensitivity to hyaluronidase or to any of its excipients. Patients with known hypersensitivity to hyaluronidase or to any of its excipients. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the labeling: Hypersensitivity and Administration-Related Reactions [see Warnings and Precautions (5.1) ] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.2) ] Venous Thromboembolic Events with Concomitant Use with Lazertinib [see Warnings and Precautions (5.3) ] Dermatologic Adverse Reactions [see Warnings and Precautions (5.4) ] Ocular Toxicity [see Warnings and Precautions (5.5) ] RYBREVANT FASPRO in Combination with Lazertinib The most common adverse reactions (≥ 20%) were rash, nail toxicity, musculoskeletal pain, fatigue, stomatitis, edema, nausea, diarrhea, vomiting, constipation, decreased appetite, and headache. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased lymphocyte count, decreased sodium, decreased potassium, decreased albumin, increased alanine aminotransferase, increased aspartate aminotransferase, decreased platelet count, increased gamma-glutamyl transferase, and decreased hemoglobin. (6.1) Intravenous Amivantamab in Combination with Lazertinib The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction, musculoskeletal pain, stomatitis, edema, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, and nausea. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT, and increased magnesium. ( 6.1 ) Intravenous Amivantamab in Combination with Carboplatin and Pemetrexed The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction, fatigue, nausea, stomatitis, constipation, edema, decreased appetite, musculoskeletal pain, vomiting, and COVID-19. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased neutrophils, decreased leukocytes, decreased platelets, decreased hemoglobin, decreased potassium, decreased sodium, increased alanine aminotransferase, increased gamma-glutamyl transferase, and decreased albumin. ( 6.1 ) Intravenous Amivantamab as a Single Agent The most common adverse reactions (≥ 20%) were rash, infusion-related reaction, paronychia, musculoskeletal pain, dyspnea, nausea, edema, cough, fatigue, stomatitis, constipation, vomiting, and pruritus. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were increased gamma-glutamyl transferase, decreased sodium, decreased potassium, and increased alkaline phosphatase. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. RYBREVANT FASPRO in Combination with Lazertinib The safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to RYBREVANT FASPRO in combination with lazertinib in 206 patients with previously treated locally advanced or metastatic NSCLC whose tumors have either an EGFR exon 19 deletion or an exon 21 L858R substitution mutation in PALOMA-3 [see Clinical Pharmacology (12.3) ]. Patients received RYBREVANT FASPRO (N=206) or intravenous amivantamab (N=210), both in combination with lazertinib, at the recommended dosages until disease progression or unacceptable toxicity. Among 206 patients who received RYBREVANT FASPRO in combination with lazertinib, 47% were exposed for 6 months or longer and 12% were exposed for greater than one year. The most common adverse reactions (≥ 20%) were rash, nail toxicity, musculoskeletal pain, fatigue, stomatitis, edema, nausea, diarrhea, vomiting, constipation, decreased …

8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on the mechanism of action [see Clinical Pharmacology (12.1) ] and findings in animal models, RYBREVANT FASPRO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of RYBREVANT FASPRO in pregnant women or animal data to assess the risk of RYBREVANT FASPRO in pregnancy. Disruption or depletion of EGFR in animal models resulted in impairment of embryo-fetal development including effects on placental, lung, cardiac, skin, and neural development. The absence of EGFR or MET signaling has resulted in embryo lethality, malformations, and post-natal death in animals (see Data ). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data RYBREVANT FASPRO for subcutaneous injection contains amivantamab and hyaluronidase [see Description (11) ]. Amivantamab: No animal studies have been conducted to evaluate the effects of amivantamab on reproduction and fetal development; however, based on its mechanism of action, RYBREVANT FASPRO can cause fetal harm or developmental anomalies. In mice, EGFR is critically important in reproductive and developmental processes including blastocyst implantation, placental development, and embryo-fetal/postnatal survival and development. Reduction or elimination of embryo-fetal or maternal EGFR signaling can prevent implantation, can cause embryo-fetal loss during various stages of gestation (through effects on placental development) and can cause developmental anomalies and early death in surviving fetuses. Adverse developmental outcomes were observed in multiple organs in embryos/neonates of mice with disrupted EGFR signaling. Similarly, knock out of MET or its ligand HGF was embryonic lethal due to severe defects in placental development, and fetuses displayed defects in muscle development in multiple organs. Human IgG1 is known to cross the placenta; therefore, amivantamab has the potential to be transmitted from the mother to the developing fetus. Hyaluronidase: In an embryo-fetal study, mice were dosed daily by subcutaneous injection during the period of organogenesis with hyaluronidase (recombinant human) at dose levels up to 2,200,000 U/kg, which is > 3600 times higher than the human dose. The study found no evidence of teratogenicity. Reduced fetal weight and increased numbers of fetal resorptions were observed, with no effects found at a daily dose of 360,000 U/kg, which is > 600 times higher than the human dose. In a peri-and post-natal reproduction study, mice have been dosed daily by subcutaneous injection, with hyaluronidase (recombinant human) from implantation through lactation and weaning at dose levels up to 1,100,000 U/kg, which is > 1800 times higher than the human dose. The study found no adverse effects on sexual maturation, learning and memory or fertility of the offspring. 8.2 Lactation Risk Summary There are no data on the presence of amivantamab or hyaluronidase in human milk or its effects on the breastfed child, or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to RYBREVANT FASPRO are unknown. Because of the potential for serious adverse reactions from RYBREVANT FASPRO in breastfed children, advise women not to breastfeed during treatment with RYBREVANT FASPRO and for 3 months after the last dose. 8.3 Females and Males of Reproductive Potential RYBREVANT FASPRO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiating RYBREVANT FASPRO [see …

12.1 Mechanism of Action Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies, amivantamab was able to disrupt EGFR and MET signaling functions through blocking ligand binding and, in exon 19 deletions, exon 21 L858R substitutions, and exon 20 insertion mutation models, degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells also allows for targeting of these cells for destruction by immune effector cells, such as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity (ADCC) and trogocytosis mechanisms, respectively. Hyaluronan is a polysaccharide found in the extracellular matrix of the subcutaneous tissue. It is depolymerized by the naturally occurring enzyme hyaluronidase. Unlike the stable structural components of the interstitial matrix, hyaluronan has a half-life of approximately 0.5 days. Hyaluronidase increases permeability of the subcutaneous tissue by depolymerizing hyaluronan. In the doses administered, hyaluronidase in RYBREVANT FASPRO acts transiently and locally. The effects of hyaluronidase are reversible and permeability of the subcutaneous tissue is restored within 24 to 48 hours.

11 DESCRIPTION RYBREVANT FASPRO is a fixed-combination drug product containing amivantamab and hyaluronidase (human recombinant). Amivantamab is a low-fucose human immunoglobulin G1-based bispecific antibody directed against the EGF and MET receptors, produced by mammalian cell line (Chinese Hamster Ovary [CHO]) using recombinant DNA technology that has a molecular weight of approximately 148 kDa. Hyaluronidase (human recombinant) is an endoglycosidase used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously. It is a glycosylated single-chain protein produced by CHO cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). Hyaluronidase (human recombinant) has a molecular weight of approximately 61 kDa. RYBREVANT FASPROTM (amivantamab and hyaluronidase-lpuj) injection for subcutaneous use is a sterile, preservative free, clear to opalescent and colorless to pale yellow solution supplied in a single-dose vial with a pH of 5.7. Each RYBREVANT FASPRO 10 mL single-dose vial contains 1,600 mg of amivantamab and 20,000 units of hyaluronidase (human recombinant), edetate disodium (0.18 mg), glacial acetic acid (1.9 mg), methionine (10 mg), polysorbate 80 (6 mg), sodium acetate (22.1 mg), sucrose (710 mg), and Water for Injection, USP. Each RYBREVANT FASPRO 14 mL single-dose vial contains 2,240 mg of amivantamab and 28,000 units of hyaluronidase (human recombinant), edetate disodium (0.25 mg), glacial acetic acid (2.6 mg), methionine (14 mg), polysorbate 80 (8.4 mg), sodium acetate (30.9 mg), sucrose (994 mg), and Water for Injection, USP. Each RYBREVANT FASPRO 15 mL single-dose vial contains 2,400 mg of amivantamab and 30,000 units of hyaluronidase (human recombinant), edetate disodium (0.27 mg), glacial acetic acid (2.8 mg), methionine (15 mg), polysorbate 80 (9 mg), sodium acetate (33.1 mg), sucrose (1,065 mg), and Water for Injection, USP. Each RYBREVANT FASPRO 22 mL single-dose vial contains 3,520 mg of amivantamab and 44,000 units of hyaluronidase (human recombinant), edetate disodium (0.4 mg), glacial acetic acid (4.1 mg), methionine (22 mg), polysorbate 80 (13.2 mg), sodium acetate (48.6 mg), sucrose (1,562 mg), and Water for Injection, USP.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied RYBREVANT FASPROTM (amivantamab and hyaluronidase-lpuj) injection for subcutaneous use is a sterile, preservative free, clear to opalescent and colorless to pale yellow solution supplied as follows: Strength NDC 1,600 mg amivantamab and 20,000 units hyaluronidase per 10 mL (160 mg and 2,000 units per mL) NDC 57894-510-01 2,240 mg amivantamab and 28,000 units hyaluronidase per 14 mL (160 mg and 2,000 units per mL) NDC 57894-514-01 2,400 mg amivantamab and 30,000 units hyaluronidase per 15 mL (160 mg and 2,000 units per mL) NDC 57894-515-01 3,520 mg amivantamab and 44,000 units hyaluronidase per 22 mL (160 mg and 2,000 units per mL) NDC 57894-522-01 Storage and Handling Store RYBREVANT FASPRO vials in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F) in original carton to protect from light. Do not freeze. Do not shake.