Amivantamab Approved for EGFR Exon 20+ NSCLC


The first targeted therapy for EGFR exon 20 insertion mutation–positive non–small cell lung cancer is now available for patients in the United States.

Amivantamab-vmjw (Rybrevant) was approved by the FDA as the first agent to treat adult patients with non–small cell lung cancer (NSCLC) whose tumors harbor EGFR exon 20 insertion mutations.

The Guardant360 CDx assay was also approved in tandem as a companion diagnostic for the agent in this indication.

“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,” 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, said in a press release. “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.”

In January, data from the phase 1 CHRYSALIS trial (NCT02609776) were presented at the 2020 World Conference on Lung Cancer (WCLC) Singapore showing that, in patients with EGFR exon 20–mutant NSCLC (n = 81), amivantamab induced an objective response in 40% of patients with 47% maintaining their response for at least 6 months and 47% remaining on therapy after a median follow-up of over 9 months.

In total, there were 3 complete responses and 29 partial responses, with a median duration of response of 11.1 months (95% CI, 6.9-not reached [NR]). Stable disease was noted in 39 patients (48%), for a clinical benefit rate of 74% (95% CI, 63%-83%). Eight patients (10%) had progressive disease. The median progression-free survival (PFS) was 8.3 months (95% CI, 6.5-10.9) and the median overall survival (OS) was 22.8 months (95% CI, 14.6%-NR).

Treatment-related adverse effects (TRAEs) occurred in almost all patients, with 16% of patients experiencing these at grade 3 or greater severity. Serious TRAEs were seen in 9% of patients, and 4% had treatment-related events that led to discontinuation. Dose reductions and interruptions deemed as related to therapy occurred at rates of 13% and 21%, respectively.

The study comprised dose-escalation and -expansion portions, with the recommended phase 2 dose (RP2D) of 1050 mg in patients weighing less than 80 kg and 1400 kg in patients 80 kg and above having been previously established in the escalation cohorts. The data presented at WCLC included patients in the post-platinum setting who harbored exon 21 insertion mutations, were treated at the RP2D for the safety analysis (n = 114), and had 3 or more disease assessments at clinical cut-off as part of the efficacy population (n = 81). The primary end point was the overall response rate.

Baseline patient demographics indicated a cohort that was majority female (59%), with a median age of 62 years (range, 42-84). Patients were equally divided between smokers (47%) and nonsmokers (53%). Forty-nine percent of patients were Asian, 37% were White, and 3% were Black. Median time from diagnosis was 17 months (range, 1-130) and previous therapies included platinum-based doublet chemotherapy in all patients, immunotherapy in 46%, and EGFR tyrosine kinase inhibitors in 25%. The median number of prior therapies was 2 (range, 1-7).

Amivantamab previously received priority review and breakthrough therapy designations from the FDA for this indication. The review of the application was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that facilitates concurrent submission and review on oncologic drugs across multiple international agencies.


FDA Approves First Targeted Therapy for Subset of Non-Small Cell Lung Cancer. News release. FDA. May 21, 2021. Accessed May 21, 2021.

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