The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:
On March 1, 2024, the Food and Drug Administration approved amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.) with carboplatin and pemetrexed for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test.
The FDA also granted traditional approval to amivantamab-vmjw for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. FDA previously granted accelerated approval for this indication.
Full prescribing information for Rybrevant will be posted here.
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-value<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) in the respective arms.
While OS results were immature at the current analysis, with 44% of pre-specified deaths for the final analysis reported, no trend towards a detriment was observed.
The most common adverse reactions (≥20%) 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 prescribing information for specific dosage information.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Brazilian Health Regulatory Agency (ANVISA) and Health Canada. The application reviews are ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application four weeks ahead of the FDA goal date.
This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncology.
