Rybrevant amivantamab-vmjw 350 mg Injection, 1 vial
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Other monoclonal antibodies and antibody drug conjugates class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Amivantamab-vmjw injection is used to treat certain types of non-small cell lung cancer (NSCLC). Amivantamab-vmjw injection is in a class of medications called bispecific antibodies. It works by helping your immune system to slow or stop the growth of cancer cells.
Read the full MedlinePlus article ↗- Rybrevant only works against lung cancer cells that have a specific change — called a mutation — in the EGFR gene. There are different types of EGFR mutations, and which one you ha...
- Why does my tumor have to be tested before I can get Rybrevant?
- Infusion-related reactions — things like flushing, chills, fever, or shortness of breath — are very common during Rybrevant infusions, especially on the very first day. The premedi...
- Why did my nurse give me so many medications before my first Rybrevant infusion?
Patient education
Supplement & herbal interactions
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 7FLD91C86K
Edetate disodium is a chemical compound that binds and removes certain metal ions. In medicines, it acts as a preservative and stabilizer by preventing metals like calcium from interfering with the product's shelf life and consistency.
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UNII 4QD397987E
An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
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UNII X573657P6P
Histidine monohydrochloride monohydrate is an amino acid salt used as a buffer in medicines. It helps maintain the proper acidity level of liquid formulations to keep the drug stable and effective.
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UNII AE28F7PNPL
Methionine is an amino acid used as a nutrient supplement and pH buffer in medicines. It helps stabilize the formulation and supports the product's overall composition.
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UNII 7T1F30V5YH
A synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together and keeps them from separating in liquid formulations.
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UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
7 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $455.18 | $455.18 / 1 injection |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9061 | $23.219 / J9061 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Rybrevant 350 mgthis 57894-0501-01 | Janssen | 1 vial | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | May 21, 2033 |
Is there a biosimilar for RYBREVANT 350 MG/7 ML VIAL?
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 57894-0501-01 You're viewing this | 1 VIAL, SINGLE-USE in 1 CARTON (57894-501-01) / 1 INJECTION in 1 VIAL, SINGLE-USE (57894-501-00) | 2021-05-21 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE RYBREVANT is a bispecific EGF receptor-directed and MET receptor-directed antibody indicated: in combination with lazertinib 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. ( 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 )
1.1First-Line Treatment of NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations RYBREVANT, 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) ] .
1.2Previously Treated NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations RYBREVANT, 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) ] .
1.3First-Line Treatment of NSCLC with EGFR Exon 20 Insertion Mutations RYBREVANT, 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) ] .
1.4Previously Treated NSCLC with EGFR Exon 20 Insertion Mutations RYBREVANT 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.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION The recommended dosage of RYBREVANT is based on baseline body weight and administered as an intravenous infusion after dilution. ( 2.3 , 2.4 ) Administer prophylactic and concomitant medications as recommended to reduce the risk of dermatologic adverse reactions. ( 2.6 ) Administer via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related reactions.
( 2.10 ) Administer RYBREVANT in combination with lazertinib or RYBREVANT as a single agent weekly for 5 weeks, with the initial dose as a split infusion in Week 1 on Day 1 and Day 2, then administer every 2 weeks starting at Week 7. ( 2.3 ) Administer RYBREVANT in combination with chemotherapy weekly for 4 weeks, with the initial dose as a split infusion in Week 1 on Day 1 and Day 2, then administer every 3 weeks starting at Week 7. ( 2.4 ) When administering RYBREVANT in combination with lazertinib, administer anticoagulant prophylaxis to reduce the risk of venous thromboembolic (VTE) events for the first four months of treatment.
( 2.7 ) Administer diluted RYBREVANT intravenously according to the infusion rates in Tables 8 and 9. ( 2.9 , 2.10 ) Body Weight (at Baseline) Dosage Recommended Dose RYBREVANT in Combination with Lazertinib or RYBREVANT as a Single Agent Less than 80 kg Weeks 1–5 Week 7 onwards 1,050 mg Greater than or equal to 80 kg Weeks 1–5 Week 7 onwards 1,400 mg RYBREVANT in Combination with Carboplatin and Pemetrexed Less than 80 kg Weeks 1–4 1,400 mg Week 7 onwards 1,750 mg Greater than or equal to 80 kg Weeks 1–4 1,750 mg Week 7 onwards 2,100 mg
2.1Important Dosage Information To reduce the risk of infusion-related reactions, administer premedications before each RYBREVANT infusion as recommended [see Dosage and Administration (2.5) ]. To reduce the risk of infusion-related reactions, administer RYBREVANT via peripheral line for Week 1 Day 1 and 2 and Week 2 [see Dosage and Administration (2.10) ]. To reduce the risk and severity of dermatologic adverse reactions with RYBREVANT, prophylactic and concomitant medications are recommended [see Dosage and Administration (2.6) ] .
To reduce the risk of venous thromboembolic (VTE) events when administering RYBREVANT in combination with lazertinib, administer anticoagulant prophylaxis for the first four months of treatment [see Dosage and Administration (2.7) ]. 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 [see Dosage and Administration (2.10) ]. When administering RYBREVANT in combination with lazertinib, administer lazertinib orally any time before the RYBREVANT infusion [see Dosage and Administration (2.10) ].
When administering RYBREVANT in combination with carboplatin and pemetrexed, infuse pemetrexed first, carboplatin second, and RYBREVANT last [see Dosage and Administration (2.10) ].
2.2Patient 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 [see Indications and Usage (1.1) ] 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) [see Indications and Usage (1.2) ] RYBREVANT in combination with carboplatin and pemetrexed First-Line Treatment of NSCLC with EGFR Exon 20 Insertion Mutations [see Indications and Usage (1.3) ] RYBREVANT in combination with carboplatin and…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 350 mg/7 mL (50 mg/mL) colorless to pale yellow solution in a single-dose vial. Injection : 350 mg/7 mL (50 mg/mL) solution in a single-dose vial ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Infusion-Related Reactions (IRR) : Interrupt infusion at the first sign of IRRs. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity. ( 2.5 , 2.8 , 5.1 ) Interstitial Lung Disease (ILD)/Pneumonitis : Monitor for new or worsening symptoms indicative of ILD.
Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. ( 2.8 , 5.2 ) Venous Thromboembolic (VTE) Events with Concomitant Use with Lazertinib: Prophylactic anticoagulation is recommended for the first four months of treatment. Monitor for signs and symptoms of VTE and treat as medically appropriate.
Withhold RYBREVANT and lazertinib based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT and lazertinib at the same dose at the discretion of the healthcare provider. Permanently discontinue RYBREVANT and continue lazertinib for recurrent VTE despite therapeutic anticoagulation.
( 2.7 , 2.8 , 5.3 ) Dermatologic Adverse Reactions : Can cause severe rash including toxic epidermal necrolysis (TEN) and acneiform dermatitis. At treatment initiation, prophylactic and concomitant medications are recommended. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity.
( 2.6 , 2.8 , 5.4 ) Ocular Toxicity : Promptly refer patients with worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity. ( 2.8 , 5.5 ) Embryo-Fetal Toxicity : Can cause fetal harm.
Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 )
5.1Infusion-Related Reactions RYBREVANT can cause infusion-related reactions (IRR) including anaphylaxis; signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour. RYBREVANT with Lazertinib RYBREVANT in combination with lazertinib can cause infusion-related reactions.
In MARIPOSA, [see Adverse Reactions (6.1) ] , IRRs occurred in 63% of patients treated with RYBREVANT in combination with lazertinib, including Grade 3 in 5% and Grade 4 in 1% of patients. The incidence of infusion modifications due to IRR was 54%, and IRRs leading to dose reduction of RYBREVANT occurred in 0.7% of patients. Infusion-related reactions leading to permanent discontinuation of RYBREVANT occurred in 4.5% of patients receiving RYBREVANT in combination with lazertinib.
RYBREVANT with Carboplatin and Pemetrexed Based on the pooled safety population [see Adverse Reactions (6.1) ] , IRR occurred in 50% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed, including Grade 3 (3.2%) adverse reactions. The incidence of infusion modifications due to IRR was 46%, and 2.8% of patients permanently discontinued RYBREVANT due to IRR. RYBREVANT as a Single Agent In CHRYSALIS, [see Adverse Reactions (6.1) ], IRR occurred in 66% of patients treated with RYBREVANT as a single agent.
Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1–2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion.
The incidence of infusion modifications due to IRR was 62%, and 1.3% of patients permanently discontinued RYBREVANT due to IRR. Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT as recommended [see Dosage and Administration (2.5) ] . Administer RYBREVANT via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related reactions [see Dosage and Administration (2.10) ] .
Monitor patients for signs and symptoms of infusion reactions during RYBREVANT…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the labeling: Infusion-Related Reactions [see Warnings and Precautions (5.1) ] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.2) ] Venous Thromboembolic Events [see Warnings and Precautions (5.3) ] Dermatologic Adverse Reactions [see Warnings and Precautions (5.4) ] Ocular Toxicity [see Warnings and Precautions (5.5) ] RYBREVANT 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 ) RYBREVANT 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 ) RYBREVANT as a Single Agent The most common adverse reactions (≥ 20%) were rash, IRR, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased phosphate, decreased potassium, increased alkaline phosphatase, increased glucose, increased gamma-glutamyl transferase, and decreased sodium. ( 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.
6.1Clinical 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 in Combination with Lazertinib The data described in the WARNINGS AND PRECAUTIONS reflect exposure to RYBREVANT in combination with lazertinib in the MARIPOSA study in 421 patients with previously untreated locally advanced or metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R substitution mutations [see Clinical Studies (14.1) ] .
Patients received RYBREVANT intravenously at 1,050 mg (for patients < 80 kg) or 1,400 mg (for patients ≥ 80 kg) once weekly for 4 weeks, then every 2 weeks thereafter starting at week 5 in combination with lazertinib, 240 mg orally once daily, until disease progression or unacceptable toxicity. Among 421 patients who received RYBREVANT in combination with lazertinib, 73% were exposed for 6 months or longer and 59% were exposed for greater than one year. The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction, edema, musculoskeletal pain, stomatitis, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, dry skin, hemorrhage, decreased appetite, pruritus, and nausea.
The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased albumin, increased ALT, decreased sodium, decreased hemoglobin, increased AST, increased GGT and increased magnesium. RYBREVANT in Combination with Carboplatin and Pemetrexed The pooled safety population described in the WARNINGS AND PRECAUTIONS also reflect exposure to RYBREVANT in combination with carboplatin and pemetrexed in 281 patients in two studies: MARIPOSA-2 [see Clinical Studies (14…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary Based on the mechanism of action and findings in animal models, RYBREVANT can cause fetal harm when administered to a pregnant woman. There are no available data on the use of RYBREVANT in pregnant women or animal data to assess the risk of RYBREVANT 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 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 No animal studies have been conducted to evaluate the effects of amivantamab-vmjw on reproduction and fetal development; however, based on its mechanism of action, RYBREVANT 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-vmjw has the potential to be transmitted from the mother to the developing fetus.
8.2Lactation Risk Summary There are no data on the presence of amivantamab-vmjw in human milk, the effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions from RYBREVANT in breast-fed children, advise women not to breastfeed during treatment with RYBREVANT and for 3 months after the last dose.
8.3Females and Males of Reproductive Potential RYBREVANT 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. Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT.
8.4Pediatric Use The safety and efficacy of RYBREVANT have not been established in pediatric patients.
8.5Geriatric Use Of the 421 patients with locally advanced or metastatic NSCLC treated with RYBREVANT in combination with lazertinib in the MARIPOSA study, 45% were ≥ 65 years of age and 12% were ≥ 75 years of age. Of the 130 patients with locally advanced or metastatic NSCLC treated with RYBREVANT in combination with carboplatin and pemetrexed in the MARIPOSA-2 study, 40% were ≥ 65 years of age and 10% were ≥ 75 years of age. Of the 151 patients with locally advanced or metastatic NSCLC treated with RYBREVANT in combination with carboplatin and pemetrexed in the PAPILLON study, 37% were ≥ 65 years of age and 8% were ≥ 75 years of age.
Of the 302 patients with locally advanced or metastatic NSCLC treated with RYBREVANT as a single agent in the CHRYSALIS study, 39% were ≥ 65 years of age and 11% were ≥ 75 years of age. No clinically important differences in safety or efficacy were observed between patients who were ≥ 65 years of age and younger patients.
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on the mechanism of action and findings in animal models, RYBREVANT can cause fetal harm when administered to a pregnant woman. There are no available data on the use of RYBREVANT in pregnant women or animal data to assess the risk of RYBREVANT 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 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 No animal studies have been conducted to evaluate the effects of amivantamab-vmjw on reproduction and fetal development; however, based on its mechanism of action, RYBREVANT 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-vmjw has the potential to be transmitted from the mother to the developing fetus.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and efficacy of RYBREVANT have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 421 patients with locally advanced or metastatic NSCLC treated with RYBREVANT in combination with lazertinib in the MARIPOSA study, 45% were ≥ 65 years of age and 12% were ≥ 75 years of age. Of the 130 patients with locally advanced or metastatic NSCLC treated with RYBREVANT in combination with carboplatin and pemetrexed in the MARIPOSA-2 study, 40% were ≥ 65 years of age and 10% were ≥ 75 years of age. Of the 151 patients with locally advanced or metastatic NSCLC treated with RYBREVANT in combination with carboplatin and pemetrexed in the PAPILLON study, 37% were ≥ 65 years of age and 8% were ≥ 75 years of age.
Of the 302 patients with locally advanced or metastatic NSCLC treated with RYBREVANT as a single agent in the CHRYSALIS study, 39% were ≥ 65 years of age and 11% were ≥ 75 years of age. No clinically important differences in safety or efficacy were observed between patients who were ≥ 65 years of age and younger patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Amivantamab-vmjw is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies amivantamab-vmjw was able to disrupt EGFR and MET signaling functions in mutation models of exon 19 deletions, exon 21 L858R substitutions, and exon 20 insertions through blocking ligand binding or 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.
Treatment with amivantamab in combination with lazertinib increased in vivo anti-tumor activity compared to either agent alone in a mouse xenograft model of human NSCLC with an EGFR L858R mutation.
12.2Pharmacodynamics The exposure-response relationship and time-course of pharmacodynamic response of amivantamab-vmjw have not been fully characterized in patients with NSCLC with EGFR mutations.
12.3Pharmacokinetics Amivantamab-vmjw exposures increased proportionally over a dosage range from 350 to 1,750 mg (0.33 to 1.7 times the lowest approved recommended dosage) when RYBREVANT was administered as a single agent. Steady-state concentrations of RYBREVANT were reached by week 13 for both the 3-week and 2-week dosing regimen and the systemic accumulation was 1.9-fold. Distribution The amivantamab-vmjw mean (%CV) volume of distribution is 5 (24%) L.
Elimination The mean (% CV) linear clearance (CL) is
0.26L/day (30%) and mean terminal half-life is 14 days (33%). Specific Populations No clinically meaningful differences in the pharmacokinetics of amivantamab-vmjw were observed based on age (range: 21–88 years), body weight (31 to 140 kg), sex, race (White, Asian or Black or African American) and ethnicity (Hispanic/Latino or not Hispanic/Latino), mild or moderate renal impairment (eGFR 30 to 89 mL/min) or mild hepatic impairment [(total bilirubin ≤ ULN and AST > ULN) or (ULN < total bilirubin ≤ 1.5 times ULN)]. The effect of severe renal impairment (eGFR 15 to 29 mL/min), end-stage renal disease (eGFR < 15 mL/min) or moderate to severe hepatic impairment (total bilirubin > 1.5 times ULN and any AST) on amivantamab-vmjw pharmacokinetics has not been studied.
Body Weight Increases in body weight increased the volume of distribution and clearance of amivantamab-vmjw. Amivantamab-vmjw exposures are 30 to 40% lower in patients who weighed ≥ 80 kg compared to patients with body weight < 80 kg at the same dose. Exposures of amivantamab-vmjw were comparable between patients who weighed < 80 kg and received 1,050 mg dose and patients who weighed ≥ 80 kg and received 1,400 mg dose.
12.6Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies (ADA) in the studies described below with the incidence of anti-drug antibodies in other studies, including those of amivantamab-vmjw or amivantamab products. During treatment in studies CHRYSALIS, CHRYSALIS-2, PAPILLON, MARIPOSA, and MARIPOSA-2 (up to 39 months), 4 of the 1,862 (0.2%) patients who received RYBREVANT as a single agent or in combination developed a treatment-emergent anti-amivantamab-vmjw antibodies.
Given the low occurrence of anti-drug antibodies, the effect of these antibodies on the pharmacokinetics, safety or efficacy of RYBREVANT is unknown.
🧬 Mechanism of Action ▾
12.1Mechanism of Action Amivantamab-vmjw is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies amivantamab-vmjw was able to disrupt EGFR and MET signaling functions in mutation models of exon 19 deletions, exon 21 L858R substitutions, and exon 20 insertions through blocking ligand binding or 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.
Treatment with amivantamab in combination with lazertinib increased in vivo anti-tumor activity compared to either agent alone in a mouse xenograft model of human NSCLC with an EGFR L858R mutation.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied RYBREVANT ® (amivantamab-vmjw) injection is a sterile, preservative-free, colorless to pale yellow solution for intravenous infusion. Each single-dose vial contains 350 mg/7 mL (50 mg/mL) RYBREVANT. Each vial is individually packed in a single carton. (NDC 57894-501-01). Storage and Handling Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze.
📦 Storage and Handling ▾
Storage and Handling Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze.
📋 Description ▾
11 DESCRIPTION Amivantamab-vmjw 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. RYBREVANT ® (amivantamab-vmjw) injection for intravenous infusion is a sterile, preservative-free, colorless to pale yellow solution in single-dose vials. The pH is 5.7.
Each RYBREVANT vial contains 350 mg (50 mg/mL) amivantamab-vmjw, EDTA disodium salt dihydrate (0.14 mg), L-histidine (2.3 mg), L-histidine hydrochloride monohydrate (8.6 mg), L-methionine (7 mg), polysorbate 80 (4.2 mg), sucrose (595 mg), and water for injection, USP.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Infusion-Related Reactions Advise patients that RYBREVANT can cause infusion-related reactions (IRR), including anaphylaxis. Instruct patients to take glucocorticoids 48 hours prior to the first RYBREVANT infusion to reduce the risk of IRR [see Dosage and Administration (2.5) ].
The majority of infusion-related reactions occurred with the first infusion. Advise patients to alert their healthcare provider immediately for any signs or symptoms of infusion-related reactions [see Warnings and Precautions (5.1) ] . Interstitial Lung Disease/Pneumonitis Advise patients of the risks of interstitial lung disease (ILD)/pneumonitis.
Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms [see Warnings and Precautions (5.2) ] . Venous Thromboembolic Events with Concomitant Use with Lazertinib When RYBREVANT is used in combination with lazertinib, advise patients of the risks of serious and life threatening venous thromboembolic (VTE) events, including deep venous thrombosis and pulmonary embolism. Advise patients that prophylactic anticoagulants are recommended to be used for the first four months of treatment.
Advise patients to immediately contact their healthcare provider for signs and symptoms of venous thromboembolism [see Warnings and Precautions (5.3) ] . Dermatologic Adverse Reactions Advise patients of the risk of dermatologic adverse reactions. Advise patients that prophylactic oral antibiotics are recommended starting on Day 1 for the first 12 weeks of treatment and, after completion of oral antibiotic treatment, topical antibiotic lotion to the scalp for the next 9 months of treatment.
Advise patients to use a non-comedogenic skin moisturizer (ceramide-based or other formulations that provide long-lasting skin hydration and exclude drying components) on the face and whole body (except scalp) and 4% chlorhexidine solution to wash hands and feet, while on treatment. Advise patients to limit direct sun exposure during and for 2 months after treatment, to wear protective clothing, and to use broad-spectrum UVA/UVB sunscreen to reduce the risk and severity of dermatologic adverse reactions [see Warnings and Precautions (5.4) ] .
Ocular Toxicity Advise patients of the risk of ocular toxicity. Advise patients to contact their ophthalmologist if they develop eye symptoms and advise discontinuation of contact lenses until symptoms are evaluated [see Warnings and Precautions (5.5) ] . Paronychia/Nail Toxicity Advise patients of the risk of paronychia.
Advise patients to contact their healthcare provider for signs or symptoms of paronychia [see Adverse Reactions (6.1) ]. Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus, to use effective contraception during treatment with RYBREVANT and for 3 months after the last dose, and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.6) , Use in Specific Populations (8.1 , 8.3) ]. Lactation Advise women not to breastfeed during treatment with RYBREVANT and for 3 months after the last dose [see Use in Specific Populations (8.2) ] .