RYBREVANT / Amivantamab-vmjw is FDA approved Bispecific Antibodies Immunotherapy For Non-Small Cell Lung Cancer
RYBREVANT / 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.
Indication of RYBREVANT/Amivantamab:
RYBREVANT/Amivantamab is a bispecific EGF receptor-directed and MET receptor directed antibody indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Warning & Precautions
Infusion-Related Reactions (IRR): Interrupt infusion at the first sign of IRRs. Reduce infusion rate or permanently discontinue RYBREVANT based on severity.
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.
Dermatologic Adverse Reactions: May cause rash including acneiform dermatitis and toxic epidermal necrolysis. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity.
Ocular Toxicity: Promptly refer patients with worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT 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 reaction associated with RYBREVANT/Amivantamab:
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.
Formulation of RYBREVANT (amivantamab-vmjw):
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.
Mechanism of Action of Amibvantamab:
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 through blocking ligand binding and, in 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.
Pharmacodynamics
The exposure-response relationship and time-course of pharmacodynamic response of amivantamab-vmjw have not been fully characterized in patients with NSCLC with EGFR exon 20 insertion mutations.
Pharmacokinetics
Amivantamab-vmjw exposures increased proportionally over a dosage range from 350 to 1750 mg (0.25 to 1.25 times the maximum approved recommended dosage).
Steady state of amivantamab-vmjw concentrations was achieved by the 9th infusion. The accumulation ratio at steady state was 2.4. Distribution The amivantamab-vmjw mean (± SD) volume of distribution is 5.13 (± 1.78) L. Elimination The mean (± SD) clearance of amivantamab-vmjw is 360 (± 144) mL/day and the terminal half-life is 11.3 (± 4.53) days