FDA Approves Amivantamab as First Agent for EGFR Exon 20-Positive NSCLC

The FDA has granted approval to amivantamab-vmjw for the frontline treatment of adult patients with non-small cell lung cancer whose tumors have EGFR exon 20 insertion mutations.

The FDA has granted approval to amivantamab-vmjw (Rybrevant) for the the treatment of adult patients with non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 20 insertion mutations, according to a press release issued by the FDA.1

Amivantamab is officially the first targeted therapy approved by the FDA to treat this subgroup of patients. The regulatory body simultaneously granted approval to the Guardant360 CDx as a companion diagnostic to identify patients with EGFR exon 20 insertion who may benefit from treatment with amivantamab.

"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."

Data from the phase 1 CHRYSALIS clinical trial (NCT02609776), which was a multicenter, open-label, multicohort study evaluating the safety and efficacy of amivantamab as a single agent and in combination with the novel third-generation EGFR tyrosine kinase inhibitor lazertinib (YH25448), supported the biologics license application for the agent.2

The coprimary end points of the study included the number of patients with adverse events, objective response rate (ORR), duration of response (DOR), and the clinical benefit rate (CBR).

At baseline, patients were largely female (59%) and a median age of 62 years (range, 42-84). Forty-seven percent were smokers while 53% were nonsmokers. In terms of race, 49% of patients were Asian, 37% were White, and 3% were Black. Previous therapies were platinum-based doublet chemotherapy in 100% of patients, immunotherapy in 46%, and EGFR TIKs in 25%. The median number of prior therapies was 2 (range, 1-7)

Results showed that at a median follow-up of 9.7 months (range, 1.1-29.3), amivantamab achieved an ORR of 40% (95% CI, 29%-51%), which included 3 complete responses and 29 partial responses. The DOR observed with the agent was 11.1 month (95% CI, 6.9-not reached [NR]). Stable disease was noted in 39 patients (48%), for a CBR of 74% (95% CI, 63%-83%), and 8 (10%) had progressive disease.

Sixty-three patients had EGFR exon insertions mutations detectable by circulating tumor DNA, and in those patients, there were 25 distinct variants found in the helical (n = 1), near loop (n = 54), and far loop (n = 8) regions. However, these variants did not impact response.

The median PFS observed was 8.3 months (95% CI, 6.5-10.9), and the median OS was 22.8 months (95% CI, 14.6%-NR).

In terms of safety, treatment-related adverse events (TRAEs) occurred in most of the study population. Sixteen percent of patients had grade 3 or greater TRAEs, and serious TRAEs were seen in 9%. TRAEs that led to discontinuation were found in 4% of patients, and dose reductions and interruptions considered to be related to therapy occurred in 13% and 21% of patients, respectively.

Overall, the safety profile of amivantamab in this study was consistent with previous reports from similar EGFR and MET inhibitors. The most common TRAEs of any grade related to EGFR inhibition were rash (86%), paronychia (42%), stomatitis (18%), and pruritis (17%); those related to the MET pathway were hypoalbuminemia (15%) and peripheral edema (10%).


1. FDA approves first targeted therapy for subset of non-small cell lung cancer. News release. FDA. May 21, 2021. Accessed May 21, 2021. https://bit.ly/3fCjEyT

2. Sabari JK, Shu CA, Park K, et al. Amivantamab in post-platinum EGFR Exon 20 insertion mutant non–small cell lung cancer. Presented at: IASLC 2020 World Conference on Lung Cancer Singapore. January 28-31, 2021. Abstract OA04.04

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