Amivantamab-vmjw

Amivantamab-vmjw
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]

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Overview

Amivantamab-vmjw is a bispecific EGF receptor that is FDA approved for the 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.

• 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.
• 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.
• 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.. Common adverse reactions include ====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, nausea, and ocular toxicity.
• 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.

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.
• 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.

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.
• 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..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Amivantamab-vmjw FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Amivantamab-vmjw in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Amivantamab-vmjw in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Amivantamab-vmjw FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Amivantamab-vmjw in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Amivantamab-vmjw in pediatric patients.

Contraindications

There is limited information regarding Amivantamab-vmjw Contraindications in the drug label.

Warnings

Infusion-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, , 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, 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, 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.
  • Administer RYBREVANT via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related reactions.
  • Monitor patients for signs and symptoms of infusion reactions during RYBREVANT infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity.If an anaphylactic reaction occurs, permanently discontinue RYBREVANT.

Interstitial Lung Disease/Pneumonitis

• RYBREVANT can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.
• RYBREVANT with Lazertinib

In MARIPOSA , ILD/pneumonitis occurred in 3.1% of patients treated with RYBREVANT in combination with lazertinib, including Grade 3 in 1% and Grade 4 in 0.2% of patients. There was one fatal case of ILD/pneumonitis and 2.9% of patients permanently discontinued RYBREVANT and lazertinib due to ILD/pneumonitis.

• RYBREVANT with Carboplatin and Pemetrexed

Based on the pooled safety population,ILD/pneumonitis occurred in 2.1% treated with RYBREVANT in combination with carboplatin and pemetrexed with 1.8% of patients experiencing Grade 3 *ILD/pneumonitis. 2.1% discontinued RYBREVANT due to ILD/pneumonitis.

• RYBREVANT as a Single Agent
• In CHRYSALIS, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT as a single agent, with 0.7 % of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) permanently discontinued RYBREVANT due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Venous Thromboembolic (VTE) Events with Concomitant Use of RYBREVANT and Lazertinib

• RYBREVANT in combination with lazertinib can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism. The majority of these events occurred during the first four months of therapy.
• In MARIPOSA VTEs occurred in 36% of patients receiving RYBREVANT in combination with lazertinib, including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of RYBREVANT, 1% of patients had VTE leading to dose reductions of RYBREVANT, and 3.1% of patients had VTE leading to permanent discontinuation of RYBREVANT. The median time to onset of VTEs was 84 days (range: 6 to 777). Administer prophylactic anticoagulation for the first four months of treatment.
• The use of Vitamin K antagonists is not recommended. Monitor for signs and symptoms of VTE events 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 level at the discretion of the healthcare provider .In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT. Treatment can continue with lazertinib at the same dose level at the discretion of the healthcare provider]. Refer to the lazertinib prescribing information for recommended lazertinib dosage modification.

Dermatologic Adverse Reactions

• RYBREVANT can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus, and dry skin.
• RYBREVANT with Lazertinib

In MARIPOSA, rash occurred in 86% of patients treated with RYBREVANT in combination with lazertinib, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose interruptions of RYBREVANT occurred in 37% of patients, rash leading to dose reductions of RYBREVANT occurred in 23% of patients, and rash leading to permanent discontinuation of RYBREVANT occurred in 5% of patients. RYBREVANT with Carboplatin and Pemetrexed Based on the pooled safety population, rash occurred in 82% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed, including Grade 3 (15%) adverse reactions. Rash leading to dose reductions occurred in 14% of patients, and 2.5% permanently discontinued *RYBREVANT and 3.1% discontinued pemetrexed. RYBREVANT as a Single Agent

• In CHRYSALIS , rash occurred in 74% of patients treated with RYBREVANT as a single agent, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT was permanently discontinued due to rash in 0.7% of patients.
• Toxic epidermal necrolysis (TEN) occurred in one patient (0.3%) treated with RYBREVANT as a single agent.

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream is recommended for dry skin.

• When initiating treatment with RYBREVANT, administer alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream 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. If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity.

Ocular Toxicity

• RYBREVANT can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus, and uveitis.
• RYBREVANT with Lazertinib

In MARIPOSA , ocular toxicity occurred in 16% of patients treated with RYBREVANT in combination with lazertinib, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Withhold, reduce the dose, or permanently discontinue RYBREVANT and continue lazertinib based on severity.

• • RYBREVANT with Carboplatin and Pemetrexed

Based on the pooled safety population ocular toxicity occurred in 16% of patients treated with *8RYBREVANT in combination with carboplatin and pemetrexed. All events were Grade 1 or 2. RYBREVANT as a Single Agent

• In CHRYSALIS, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with *RYBREVANT. All events were Grade 1–2.

Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity.

Embryo-Fetal Toxicity

• Based on its mechanism of action and findings from animal models, RYBREVANT can cause fetal harm when administered to a pregnant woman.
• Administration of other EGFR inhibitor molecules to pregnant animals has resulted in an increased incidence of impairment of embryo-fetal development, embryo lethality, and abortion. Advise females of reproductive potential of the potential risk to the fetus.
• Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT.

Adverse Reactions

Clinical Trials Experience

The following adverse reactions are discussed elsewhere in the labeling:

• Infusion-Related Reactions.
• Interstitial Lung Disease/Pneumonitis.
• Venous Thromboembolic Events.
• Dermatologic Adverse Reactions.
• Ocular Toxicity.

• 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 . 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, nausea, and ocular toxicity. 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 in 130 patients with previously treated 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 osimertinib.
• PAPILLON in 151 patients with previously untreated, locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.
• Patients received RYBREVANT intravenously at 1,400 mg (for patients < 80 kg) or 1,750 mg (for patients ≥ 80 kg) once weekly through 4 weeks, then every 3 weeks with a dose of 1,750 mg (for patients < 80 kg) or 2,100 mg (for patients ≥ 80 kg) starting at Week 7 until disease progression or unacceptable toxicity, in combination with carboplatin at area under the curve AUC 5 once every 3 weeks, for up to 12 weeks, and pemetrexed at 500 mg/m2 once every 3 weeks until disease progression or unacceptable toxicity. Among 281 patients who received RYBREVANT in combination with carboplatin and pemetrexed, 65% were exposed for 6 months or longer and 24% were exposed for greater than one year. In the safety population, the most common (≥ 20%) adverse reactions were rash, nail toxicity, infusion-related reaction, fatigue, nausea, stomatitis, constipation, edema, decreased appetite, musculoskeletal pain, vomiting, and COVID-19. The most common Grade 3 to 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.

RYBREVANT as a Single Agent

• The data in the WARNINGS AND PRECAUTIONS also reflect exposure to RYBREVANT as a single agent in CHRYSALIS in 302 patients with locally advanced or metastatic NSCLC.
• Patients received RYBREVANT at 1,050 mg (for patient baseline body weight < 80 kg) or 1,400 mg (for patient baseline body weight ≥ 80 kg) once weekly for 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity. Among 302 patients who received RYBREVANT as a single agent, 36% were exposed for 6 months or longer and 12% were exposed for greater than one year. In the safety population, the most common (≥ 20%) adverse reactions were rash, infusion-related reaction, paronychia, musculoskeletal pain, dyspnea, nausea, edema, cough, fatigue, stomatitis, constipation, vomiting and pruritus. The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were increased gamma glutamyl transference, decreased sodium, decreased potassium and increased alkaline phosphatase.

First-line Treatment of NSCLC with Exon 19 deletions or Exon 21 L858R substitution mutations

• The safety data described below reflect exposure to RYBREVANT in combination with lazertinib in 421 previously untreated patients with locally advanced or metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R substitution mutation in the MARIPOSA .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. Among the 421 patients who received RYBREVANT in combination with lazertinib, 73% were exposed to RYBREVANT for ≥ 6 months and 59% were exposed to RYBREVANT for > 1 year.
• The median age of patients who received RYBREVANT in combination with lazertinib was 64 years (range: 25 to 88); 64% were female; 59% were Asian, 38% were White, 1.7% were American Indian or Alaska Native, 0.7% were Black or African American, 1% were of unknown or other races; and 13% were Hispanic or Latino, 67% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1, 33% had ECOG PS of 0, 60% had EGFR exon 19 deletions, and 40% had EGFR exon 21 L858R substitution mutations.
• Serious adverse reactions occurred in 49% of patients who received RYBREVANT in combination with lazertinib. Serious adverse reactions occurring in ≥ 2% of patients included VTE (11%), *pneumonia (4%), rash, and ILD/pneumonitis (2.9% each), COVID-19 (2.4%), pleural effusion and infusion-related reaction (2.1% each). Fatal adverse reactions occurred in 7% of patients who received RYBREVANT in combination with lazertinib due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each).
• Permanent discontinuation of RYBREVANT due to an adverse reaction occurred in 34% of patients. Adverse reactions which resulted in permanent discontinuation in ≥ 1% of patients included rash, infusion-related reactions, nail toxicity, VTE, ILD/pneumonitis, pneumonia, edema, hypoalbuminemia, fatigue, paresthesia and dyspnea.
• Dosage interruption of RYBREVANT due to an adverse reaction occurred in 88% of patients. Adverse reactions which required dosage interruption in ≥5% of patients were infusion-related reactions, rash, nail toxicity, COVID-19, VTE, increased ALT, edema, and hypoalbuminemia.
• Dose reductions of RYBREVANT due to an adverse reaction occurred in 46% of patients. Adverse reactions requiring dose reductions in ≥ 5% of patients were rash and nail toxicity.
• 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. 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.

Table 10 summarizes the adverse reactions (≥ 10%) in MARIPOSA.

summarizes the adverse reactions (≥ 10%) in MARIPOSA.

summarizes the adverse reactions (≥ 10%) in MARIPOSA.

Clinically relevant adverse reactions in < 10% of patients who received RYBREVANT in combination with lazertinib included ILD/pneumonitis (3.1%). Table 11 summarizes the laboratory abnormalities in MARIPOSA.

Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with NSCLC with EGFR Exon 19 Deletion or Exon 21 L858R Substitution Mutations in MARIPOSA

Previously Treated Non-Small Cell Lung Cancer (NSCLC) with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations

• The safety data described below reflect exposure to RYBREVANT in combination with carboplatin and pemetrexed was evaluated in MARIPOSA-2 .
• Eligible patients had locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations with progressive disease on or after treatment with osimertinib .Patients with asymptomatic or previously treated and stable intracranial metastases were eligible. Patients received RYBREVANT intravenously at 1,400 mg (for patients < 80 kg) or 1,750 mg (for patients ≥ 80 kg) once weekly through 4 weeks, then every 3 weeks with a dose of 1,750 mg (for patients < 80 kg) or 2,100 mg (for patients ≥ 80 kg) starting at Week 7 until disease progression or unacceptable toxicity, in combination with carboplatin at area under the curve AUC 5 once every 3 weeks, for up to 12 weeks, and pemetrexed at 500 mg/m 2once every 3 weeks until disease progression or unacceptable toxicity. Among patients who received RYBREVANT (n=130), 52% were exposed for 6 months or longer and 7% were exposed for greater than one year. The median treatment duration was 6.3 months (range: 0 to 14.7 months).
• The median age was 62 years (range: 36 to 84 years); 62% were female; 48% were Asian, 46% were White, 2.3% Black or African American, 1.5% race not reported, 1.5% race unknown, 0.8% Alaska native; 7% were Hispanic or Latino; and 87% had baseline body weight < 80 kg.
• Serious adverse reactions occurred in 32% of patients who received RYBREVANT in combination with carboplatin and pemetrexed. Serious adverse reactions in > 2% of patients included dyspnea (3.1%), thrombocytopenia (3.1%), sepsis (2.3%), and pulmonary embolism (2.3%). Fatal adverse reactions occurred in 2.3% of patients who received RYBREVANT in combination with carboplatin and pemetrexed; these included respiratory failure, sepsis, and ventricular fibrillation (0.8% each).
• Permanent discontinuation of RYBREVANT due to adverse reactions occurred in 11% of patients. The most frequent adverse reactions leading to discontinuation of RYBREVANT in ≥ 5% of patients were infusion-related reactions.
• Dose interruptions of RYBREVANT due to an adverse reaction occurred in 60% of patients. Infusion-related reactions (IRR) requiring infusion interruptions occurred in 52% of patients. Adverse reactions requiring dose interruption in ≥ 5% of patients included infusion-related reaction, rash and fatigue.
• Dose reductions of RYBREVANT due to an adverse reaction occurred in 17% of patients. Adverse reactions requiring dose reductions in ≥ 2% of patients included rash.
• The most common adverse reactions ≥ 20% were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19.

Table 12 summarizes the adverse reactions in MARIPOSA-2.

Adverse Reactions (≥ 10%) in Previously Treated Patients with NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations Treated with RYBREVANT in Combination with Carboplatin and Pemetrexed in MARIPOSA-2

Adverse Reactions (≥ 10%) in Previously Treated Patients with NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations Treated with RYBREVANT in Combination with Carboplatin and Pemetrexed in MARIPOSA-2

• Clinically relevant adverse reactions in < 10% of patients who received RYBREVANT in combination with carboplatin and pemetrexed include: abdominal pain, hemorrhoids, dizziness, visual impairment, trichomegaly, keratitis, and interstitial lung disease.

Table 13 summarizes the laboratory abnormalities in MARIPOSA-2.

Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations Treated with RYBREVANT in Combination with Carboplatin and Pemetrexed in MARIPOSA-2

Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with NSCLC with EGFR Exon 19 Deletions or Exon 21 L858R Substitution Mutations Treated with RYBREVANT in Combination with Carboplatin and Pemetrexed in MARIPOSA-2

• First-line Treatment of Non-Small Cell Lung Cancer (NSCLC) with Exon 20 Insertion Mutations
• The safety data described below reflect exposure to RYBREVANT in combination with carboplatin and pemetrexed at the recommended dosage in the PAPILLON trial in 151 patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.
• Among patients who received RYBREVANT in combination with carboplatin and pemetrexed the median exposure was 9.7 months (range: 0.0 to 26.9 months). In patients that received carboplatin and pemetrexed alone, the median exposure was 6.7 months (range 0.0 to 25.3).
• The median age was 61 years (range: 27 to 86 years); 56% were female; 64% were Asian, 32% were White, 1.3% were Black or African American, race was not reported in 1.3% of patients; 89% were not Hispanic or Latino; 86% had baseline body weight < 80 kg.
• Serious adverse reactions occurred in 37% of patients who received RYBREVANT in combination with carboplatin and pemetrexed. Serious adverse reactions in ≥ 2% of patients included rash, pneumonia, interstitial lung disease (ILD), pulmonary embolism, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified.
• Permanent discontinuation of RYBREVANT due to an adverse reaction occurred in 11% of patients. Adverse reactions resulting in permanent discontinuation of RYBREVANT in ≥ 1% of patients were rash and ILD.
• Dose interruptions of RYBREVANT due to an adverse reaction occurred in 64% of patients. Infusion-related reactions (IRR) requiring infusion interruptions occurred in 38% of patients. Adverse reactions requiring dose interruption in ≥ 5% of patients included rash and nail toxicity.
• Dose reductions of RYBREVANT due to an adverse reaction occurred in 36% of patients. Adverse reactions requiring dose reductions in ≥ 5% of patients included rash and nail toxicity.
• The most common adverse reactions (≥ 20%) were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting. The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased albumin, increased alanine aminotransferase, increased gamma-glutamyl transferase, decreased sodium, decreased potassium, decreased magnesium, and decreases in white blood cells, hemoglobin, neutrophils, platelets, and lymphocytes.

Table 14 summarizes the adverse reactions in PAPILLON.

Adverse Reactions (≥ 10%) in Patients with Metastatic NSCLC with Exon 20 Insertion Mutations Who Received RYBREVANT in Combination with Carboplatin and Pemetrexed in PAPILLON

Adverse Reactions (≥ 10%) in Patients with Metastatic NSCLC with Exon 20 Insertion Mutations Who Received RYBREVANT in Combination with Carboplatin and Pemetrexed in PAPILLON

• ion with carboplatin and pemetrexed included pulmonary embolism, deep vein thrombosis, skin ulcer, conjunctivitis, and interstitial lung disease (ILD)/pneumonitis.

Table 15 summarizes the laboratory abnormalities in PAPILLON.

centreSelect Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with Metastatic NSCLC with EGFR Exon 20 Insertion Mutations Who Received RYBREVANT in Combination with Carboplatin and Pemetrexed in PAPILLON

• Previously Treated NSCLC Exon 20 Insertion Mutations
• The safety data described below reflect exposure to RYBREVANT at the recommended dosage in 129 patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations in the CHRYSALIS trial, whose disease had progressed on or after platinum-based chemotherapy. Among patients who received RYBREVANT, 44% were exposed for 6 months or longer and 12% were exposed for greater than one year.

The median age was 62 years (range: 36 to 84 years); 61% were female; 55% were Asian, 35% were White, and 2.3% were Black; and 82% had baseline body weight < 80 kg.

• Serious adverse reactions occurred in 30% of patients who received RYBREVANT. Serious adverse reactions in ≥ 2% of patients included pulmonary embolism, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death.
• Permanent discontinuation of RYBREVANT due to an adverse reaction occurred in 11% of patients. Adverse reactions resulting in permanent discontinuation of RYBREVANT in ≥ 1% of patients were pneumonia, IRR, pneumonitis/ILD, dyspnea, pleural effusion, and rash.
• Dose interruptions of RYBREVANT due to an adverse reaction occurred in 78% of patients. Infusion-related reactions (IRR) requiring infusion interruptions occurred in 59% of patients. Adverse reactions requiring dose interruption in ≥ 5% of patients included dyspnea, nausea, rash, vomiting, fatigue, and diarrhea.
• Dose reductions of RYBREVANT due to an adverse reaction occurred in 15% of patients. Adverse reactions requiring dose reductions in ≥ 2% of patients included rash and paronychia.
• The most common adverse reactions (≥ 20%) were rash, IRR, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting. The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased phosphate, decreased potassium, increased glucose, increased alkaline phosphatase, increased gamma-glutamyl transferase, and decreased sodium.

Table 16 summarizes the adverse reactions in CHRYSALIS.

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• Clinically relevant adverse reactions in < 10% of patients who received RYBREVANT included ocular toxicity, ILD/pneumonitis, and toxic epidermal necrolysis (TEN).

Table 17 summarizes the laboratory abnormalities in CHRYSALIS.

Postmarketing Experience

Postmarketing Experience

• The following adverse reactions associated with the use of RYBREVANT were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Immune System disorders:Infusion-related reactions, including anaphylaxis/anaphylactic reactions.

Drug Interactions

There is limited information regarding Amivantamab-vmjw Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

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.

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Amivantamab-vmjw in women who are pregnant.

Labor and Delivery

• RYBREVANT can cause fetal harm when administered to a pregnant woman.

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.

Nursing Mothers

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.

Pediatric Use

The safety and efficacy of RYBREVANT have not been established in pediatric patients.

Geriatic 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.

Gender

There is no FDA guidance on the use of Amivantamab-vmjw with respect to specific gender populations.

Race

There is no FDA guidance on the use of Amivantamab-vmjw with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Amivantamab-vmjw in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Amivantamab-vmjw in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Amivantamab-vmjw in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Amivantamab-vmjw in patients who are immunocompromised.

Administration and Monitoring

Administration

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.

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.

File:Rbyt2.png

Recommended Dosage for RYBREVANT in Combination with Carboplatin and Pemetrexed

Dose adjustment is not required for subsequent body weight changes. The recommended order of administration and regimen for RYBREVANT in combination with carboplatin and pemetrexed are provided in Table 3.

File:Rbyt3.png

Order of Administration and Regimen for RYBREVANT in Combination with Carboplatin and Pemetrexed

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.

File:Rbyt4.png

Recommended Dosage Schedule for RYBREVANT in Combination with Lazertinib or RYBREVANT as a Single Agent

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
• .Administer both antihistamine and antipyretic prior to all infusions.

File:Rbyt5.png

Premedications

Dosage Modifications for Adverse Reactions

The recommended dose reductions for adverse reactions for RYBREVANT are listed in Table 6.

File:Rbyt6.png

Dose Reductions for Adverse Reactions for RYBREVANT

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

Recommended Dosage Modifications and Management for Adverse Reactions for RYBREVANT

Recommended Dosage Modifications and Management for Adverse Reactions for RYBREVANT

Recommended Dosage Modifications and Management for Adverse Reactions for RYBREVANT

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, mustbe 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

Infusion Rates of RYBREVANT in Combination with Carboplatin and Pemetrexed for Treatment of NSCLC

Infusion Rates of RYBREVANT in Combination with Lazertinib or RYBREVANT as Single Agent

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

Infusion Rates of RYBREVANT in Combination with Lazertinib or RYBREVANT as Single Agent

Monitoring

• Interrupt RYBREVANT infusion if IRR is suspected and monitor patient until reaction symptoms resolve.
• Interrupt RYBREVANT infusion and administer supportive care medications. Continuously monitor patient until reaction symptoms resolve.

IV Compatibility

There is limited information regarding the compatibility of Amivantamab-vmjw and IV administrations.

Overdosage

There is limited information regarding Amivantamab-vmjw overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Amivantamab-vmjw Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Amivantamab-vmjw Mechanism of Action in the drug label.

Structure

There is limited information regarding Amivantamab-vmjw Structure in the drug label.

Pharmacodynamics

There is limited information regarding Amivantamab-vmjw Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Amivantamab-vmjw Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Amivantamab-vmjw Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Amivantamab-vmjw Clinical Studies in the drug label.

How Supplied

There is limited information regarding Amivantamab-vmjw How Supplied in the drug label.

Storage

There is limited information regarding Amivantamab-vmjw Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Amivantamab-vmjw Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Amivantamab-vmjw interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Amivantamab-vmjw Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Amivantamab-vmjw Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.