FDA Approval Summary: Amivantamab for the Treatment of Patients with Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

Abstract

The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) receptor, on May 21, 2021, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Approval was based on results of an ongoing, multicenter, non-randomized, open-label, multi-cohort clinical trial (CHRYSALIS, NCT 02609776), demonstrating a substantial overall response rate (ORR) and durable responses, with an ORR of 40% (95% CI: 29, 51) and a median response duration of 11.1 months (95% CI: 6.9, not evaluable). Guardant360® CDx was contemporaneously approved as a companion diagnostic for this indication to identify EGFR exon 20 insertion mutations in plasma specimens. The most notable safety finding was the high incidence (66%) of infusion-related reactions (IRRs), which is addressed in both the Dosage and Administration and Warnings and Precautions sections of the product label. Other common adverse reactions (occurring in ≥20% of patients) were rash, paronychia, musculoskeletal pain, dyspnea, nausea and vomiting, fatigue, edema, stomatitis, cough, and constipation. The approval of amivantamab was the first approval of a targeted therapy for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations.

Amivantamab: A Novel Advance in the Treatment of Non-small Cell Lung Cancer

“…These patients received the established recommended combined dose of 1050 mg IV of amivantamab (1400 mg, ≥80 kg) + oral lazertinib at a dose of 240 mg. As of April 19, 2021, 116 patients were enrolled in cohort A with an average age of 63 years, 68% female, and 60% Asian, with a median follow-up of 3.7 months, thus 17 patients from the target population, of which 10 remain in treatment with PR and seven with stable disease. The safety profile of cohort A was consistent with previously reported experience with a combined recommended dose of amivantamab plus lazertinib, and no new drug safety signals were identified [25,32].…”

Developments in predictive biomarker testing and targeted therapy in advanced stage non-small cell lung cancer and their application across European countries

“… 14 , 16 Newly developed EGFR -targeting therapies, including amivantamab and mobocertinib, have shown promising treatment results in patients with EGFR exon 20 insertion mutations. 17 , 18 , 19 , 20 , 21 In 2021, amivantamab, a bispecific anti-EGFR and anti-MET antibody, was approved by the EMA as a second-line treatment option for advanced-stage NSCLC patients with EGFR exon 20 insertion mutations, based on the results of the phase I CHRYSALIS trial. 19 …”

The Role of MET in Resistance to EGFR Inhibition in NSCLC: A Review of Mechanisms and Treatment Implications

“…In patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations who had progressed on or after platinum-based chemotherapy, an ORR of 40% (95% CI 29-51) was seen. Amivantamab received accelerated FDA approval in this setting based on these results [62].…”