On May 21, the U.S. Food and Drug Administration (FDA) granted accelerated approval to amivantamab-vmjw (Rybrevant), a bispecific antibody directed against epidermal growth factor and MET receptors, for adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) and 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.
FDA also approved the Guardant360® CDx as a companion diagnostic for amivantamab-vmjw.
Approval was based on CHRYSALIS, a multicenter, nonrandomized, open label, multicohort clinical trial (ClinicalTrials.gov identifier NCT02609776). Efficacy was evaluated in 81 patients with advanced NSCLC with EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. Patients received amivantamab-vmjw once weekly for 4 weeks and then every 2 weeks thereafter until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate according to Response Evaluation Criteria in Solid Tumors version 1.1 as evaluated by blinded independent central review and response duration. The overall response rate was 40% (95% confidence interval [CI] = 29%–51%), with a median response duration of 11.1 months (95% CI = 6.9–not evaluable).
The most common adverse reactions (≥ 20%) were rash, infusion-related reactions, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting.
The recommended dose of amivantamab-vmjw is 1,050 mg for patients with baseline body weight < 80 kg, and 1,400 mg for those with body weight ≥ 80 kg, administered weekly for 4 weeks and then every 2 weeks thereafter until disease progression or unacceptable toxicity.