Amivantamab

Common name: amivantamab

Trade name: Rybrevant

All names: amivantamab, Rybrevant, Amivantamab-vmjw

Indications:

For the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose disease has progressed after failure of platinum-containing chemotherapy and who have insertion mutations in exon 20 of the epidermal growth factor receptor (EGFR) gene.

Usage and Dosage:

Recommended dosage of RYBREVANT: Based on baseline body weight, diluted and administered as an intravenous infusion.

<80kg, 1050 mg

≥80kg, 1400 mg

Adopt preoperative medication as recommended. Administer via peripheral line during weeks 1 and 2.

Administer RYBREVANT as a weekly infusion for 4 weeks, with the initial dose administered as a divided infusion on Days 1 and 2 of Week 1, then every 2 weeks.

Adverse Reactions:

The most common adverse reactions (≥ 20%): rash, infusion-related reactions, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation and vomiting.

The most common grade 3 or 4 laboratory abnormalities (≥2%): lymphopenia, decreased albumin, decreased phosphate, decreased potassium, increased alkaline phosphatase, increased glucose, increased gamma-glutamyl transferase, and decreased sodium.

Taboos:

None.

Precautions:

amivantamab can cause skin reactions. Avoid sun exposure during treatment and for 2 months after your last dose.

Infusion-related reaction (IRR): In the event of an infusion-related reaction, the infusion should be interrupted. Reduce infusion rate or permanently discontinue amivantamab based on severity.

Interstitial Lung Disease (ILD)/Pneumonia: Monitor for new or worsening symptoms of ILD. Discontinue amivantamab immediately in patients with suspected ILD/pneumonitis or permanently if ILD/pneumonitis is confirmed.

Dermatological adverse reactions: May cause rashes, including acneiform dermatitis and toxic epidermal necrolysis.

Withhold, reduce dose, or permanently discontinue amivantamab based on severity.

Ocular toxicity: Promptly refer patients with worsening ocular symptoms to an ophthalmologist. Withhold, reduce dose, or permanently discontinue amivantamab based on severity.

Embryo-fetal toxicity: Can cause fetal harm. It is recommended that women be aware of potential risks to the fetus and take effective contraceptive measures.

Storage:

Store in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.

Don’t freeze.

Mechanism of action:

amivantamab is an EGFR/MET bispecific monoclonal antibody that can bind to the EGFR receptor and C-MET receptor on the cell surface respectively, blocking the activation of their signaling pathways and transmitting signals downstream, inhibiting the proliferation of tumor cells with related expressions.

Safety and efficacy:

The BLA and MAA of amivantamab are based on the results of the Phase I CHRYSALIS study (NCT02609776). Data show that in patients with advanced NSCLC carrying EGFR exon 20 insertion mutations, amivantamab treatment showed durable responses: (1) Among all evaluable patients, the overall response rate (ORR) was 36%, with a median response duration of The median DOR (DOR) was 10 months, and the clinical benefit rate (≥ partial response [PR] + stable disease ≥ 12 weeks) was 67%; (2) among evaluable patients who had previously received platinum-containing chemotherapy, the ORR was 41%, the median DOR was 7 months, and the clinical benefit rate was 72%.

Based on the ORR and DOR data of the CHRYSALIS study, in March this year, the US FDA granted amivantamab breakthrough drug designation (BTD) for the treatment of patients with metastatic NSCLC who have progressed after receiving platinum-containing chemotherapy and have insertion mutations in EGFR exon 20.