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Rybrevant First FDA-Approved Therapy for NSCLC with EGFR Exon 20 Insertion Mutations

On May 21, 2021, the FDA accelerated the approval of amivantamab-vmjw (Rybrevant; Janssen/Johnson & Johnson), a bispecific antibody targeting mutations in the EGFR and MET pathways, for adults with non–small-cell lung cancer (NSCLC) that is associated with EGFR exon 20 insertion mutations, as detected by the FDA-approved Guardant360 CDx test, which was approved on the same day as a companion diagnostic for amivantamab. The FDA had granted amivantamab a breakthrough therapy designation for this indication.

Amivantamab is the first drug approved by the FDA for the treatment of patients with NSCLC and EGFR exon 20 insertion mutations. Approximately 2% to 3% of patients with NSCLC have EGFR exon 20 insertion mutations, a group of mutations that causes rapid cell growth. EGFR exon 20 insertion mutations are the third most common type of EGFR mutation.

“With today’s approval, for the first time, patients with non–small-cell lung cancer with EGFR exon 20 insertion mutations will have a targeted treatment option,” said Julia Beaver, MD, Chief of Medical Oncology in the FDA’s Oncology Center of Excellence.

The FDA approved amivantamab based on a study of 81 patients with NSCLC and EGFR exon 20 insertion mutations whose disease progressed during or after platinum-based chemotherapy. The main outcome measured was overall response rate (ORR).

The ORR was 40% and the median duration of response was 11.1 months, including 63% of responses lasting ≥6 months.

The most common side effects of amivantamab include rash, infusion-related reactions, skin infections around the fingernails or toenails, muscle and joint pain, shortness of breath, nausea, fatigue, swelling in the lower legs or hands or face, sores in the mouth, cough, constipation, vomiting, and changes in certain blood tests.

Amivantamab should be withheld if patients have symptoms of interstitial lung disease and permanently discontinued in patients with confirmed disease. Patients taking amivantamab should limit sun exposure during and for 2 months after treatment. Amivantamab may cause vision problems and should not be used in pregnant women.

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