The Food and Drug Administration (FDA) has granted accelerated approval to RybrevantTM (amivantamab-vmjw) for the treatment of adults 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. The Guardant360® CDx liquid biopsy blood test was also approved as a companion diagnostic for use with Rybrevant.
Rybrevant is a fully-human bispecific antibody directed against EGFR and MET receptors. The approval was based on data from the multicenter, open-label, multi-cohort phase 1 CHRYSALIS trial (ClinicalTrials.gov: NCT02609776) that evaluated the efficacy and safety of amivantamab-vmjw in 81 patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy.
Patients received amivantamab-vmjw 1050mg (baseline body weight <80kg) or 1400mg (baseline body weight ≥80kg) as an intravenous infusion once weekly for 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity. The main outcome measure was overall response rate, according to RECIST v1.1.
Results showed an overall response rate of 40% (95% CI, 29-51), with 3.7% of patients achieving complete response and 36% having partial response. The median duration of response was 11.1 months (95% CI, 6.9-not estimable); 63% of responders had a response duration of 6 months or more.
The most common adverse reactions reported were rash, infusion-related reactions, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, vomiting and laboratory abnormalities. Treatment with Rybrevant has also been associated with interstitial lung disease (ILD)/pneumonitis, dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity.
“Advances in precision oncology continue to facilitate drug development, allowing diseases like lung cancer to be subset into biomarker-defined populations appropriate for targeted therapies,” said Julia Beaver, MD, chief of medical oncology in the FDA’s Oncology Center of Excellence and acting deputy director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “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.”
Rybrevant is supplied as 350mg/7mL solution in a single-dose vial for intravenous infusion after dilution.
- FDA approves first targeted therapy for subset of non-small cell lung cancer. [press release]. Silver Spring, MD: US Food and Drug Administration; May 21, 2021.
- Rybrevant™ (amivantamab-vmjw) receives FDA approval as the first targeted treatment for patients with non-small cell lung cancer with EGFR exon 20 insertion mutations. [press release]. Horsham, PA: Janssen Biotech, Inc.; May 21, 2021.
- Rybrevant [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2021.