Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) for subcutaneous injection

Initial US Approval:

2025

Key Clinical Studies:

PALOMA-3

Drug Class/Description:

combination of amivantamab, a bispecific EGF receptor-directed and MET receptor-directed antibody, and hyaluronidase, an endoglycosidase

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. 
• 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. 

Dosage and Administration:

For subcutaneous use only.

• RYBREVANT FASPRO has different recommended dosage and administration than intravenous amivantamab products.
• Administer each injection of RYBREVANT FASPRO subcutaneously in the abdomen over approximately 5 minutes.
• The recommended dosage of RYBREVANT FASPRO is based on baseline body weight. (2.3) • Administer premedications as recommended. 
• Recommended dosage for RYBREVANT FASPRO in combination with carboplatin and pemetrexed (every 3-week dosing), see Table 2.
• Recommended dosage for RYBREVANT FASPRO in combination with lazertinib or  for RYBREVANT FASPRO as a single agent (every 2-week dosing), see Table 4. 

Dosage Forms and Strengths:

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.

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. 

Contraindications:

Patients with known hypersensitivity to hyaluronidase or to any of its excipients. 

Warnings and Precautions:

• Hypersensitivity and Administration-Related Reactions (ARR): Premedicate with antihistamines, antipyretics, and glucocorticoids. Monitor patients for any signs and symptoms of ARRs. Resume treatment upon resolution of symptoms or permanently discontinue RYBREVANT FASPRO based on severity.
• Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening symptoms indicative of ILD/pneumonitis. Immediately withhold RYBREVANT FASPRO in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.
• 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 FASPRO and lazertinib based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT FASPRO and lazertinib at the same dose at the discretion of the healthcare provider. Permanently discontinue RYBREVANT FASPRO and continue lazertinib for recurrent VTE despite therapeutic anticoagulation.
• Dermatologic Adverse Reactions: Can cause severe rash including toxic epidermal necrolysis (TEN) and dermatitis acneiform. At treatment initiation, prophylactic and concomitant medications are recommended. Withhold, dose reduce or permanently discontinue RYBREVANT FASPRO based on severity.
• Ocular Toxicity: Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT FASPRO based on severity.
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. 

Adverse Reactions:

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.
• 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.

Intravenous Amivantamab in Combination with Lazertinib

• The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusionrelated 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. 

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.
• 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.

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. 
• The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were increased gamma-glutamyl transferase, decreased sodium, decreased potassium, and increased alkaline phosphatase. 

Use in Specific Populations:

Lactation: Advise not to breastfeed. 

Adapted From:

https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT+Faspro-pi.pdf

 

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