FDA Approves Amivantamab-Vmjw for EGFR Exon 20 Insertion–Variant NSCLC

It also gave amivantamab-vmjw traditional approval for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion variants, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. FDA previously granted (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-amivantamab-vmjw-metastatic-non-small-cell-lung-cancer) accelerated approval for the indication.

Efficacy was evaluated in PAPILLON (NCT04538664), a randomized, open-label multicenter trial of 308 patients with EGFR exon 20 insertion mutations. Patients were randomized 1:1 to receive amivantamab-vmjw with carboplatin and pemetrexed or carboplatin and pemetrexed.

The major efficacy outcome measure was progression-free survival (PFS), as assessed by blinded independent central review (BICR), with overall survival (OS) as a key secondary outcome measure. Amivantamab-vmjw plus carboplatin and pemetrexed demonstrated a statistically significant improvement in PFS compared with carboplatin and pemetrexed with a hazard ratio of 0.40 (95% CI = 0.30, 0.53; p < 0.0001). The median PFS was 11.4 months (95% CI = 9.8, 13.7) and 6.7 months (95% CI = 5.6, 7.3), respectively. OS results were immature at the time of analysis, with 44% of the final analysis’s prespecified deaths reported, but researchers did not observe a trend toward a detriment.

The most common adverse reactions reported in at least 20% of patients receiving amivantamab-vmjw were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting.

The recommended amivantamab-vmjw dose is based on body weight. See the full prescribing information (https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761210s003lbl.pdf) for specific dosage information.

FDA’s review was conducted under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an initiative of the Oncology Center of Excellence (OCE), which provides a framework for concurrent submission and review of oncology drugs among international partners. FDA also collaborated with the Brazilian Health Regulatory Agency and Health Canada for the review, which is ongoing at the other regulatory agencies.

FDA’s review also used the Real-Time Oncology Review (https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review) (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment. The application was granted priority review, and FDA approved it four weeks ahead of its goal date. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine or device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).