Amivantamab and Hyaluronidase (human recombinant)

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…

Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies, amivantamab was able to disrupt EGFR and MET signaling functions through blocking ligand binding and, in exon 19 deletions, exon 21 L858R substitutions, and exon 20 insertion mutation models, degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells also allows for targeting of these cells for destruction by immune effector cells, such as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity (ADCC) and trogocytosis mechanisms, respectively. Hyaluronan is a polysaccharide found in the extracellular matrix of the subcutaneous tissue. It is depolymerized by the naturally occurring enzyme hyaluronidase.

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. Administer premedications as recommended. RYBREVANT FASPRO has different recommended dosages and dosing schedules based upon the indication and baseline body weight. See dosing Tables 3, 4, and 5.

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

Hypersensitivity and Administration-Related Reactions (ARR): Premedicate with antihistamines, antipyretics, and glucocorticoids. Monitor patients for any signs and symptoms of ARRs. For the first dose, monitor patients for hypersensitivity and administration-related reactions for 2 to 4 hours following the end of the injection. 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.

The following adverse reactions are discussed elsewhere in the labeling: Hypersensitivity and Administration-Related Reactions Interstitial Lung Disease/Pneumonitis Venous Thromboembolic Events with Concomitant Use with Lazertinib Dermatologic Adverse Reactions Ocular Toxicity 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.

Store RYBREVANT FASPRO vials in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F) in original carton to protect from light. Do not freeze. Do not shake.