On September 19, 2024, the Food and Drug Administration approved amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.) with carboplatin and pemetrexed for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor.

Full prescribing information for Rybrevant will be posted on Drugs@FDA.

Efficacy was evaluated in MARIPOSA-2 (NCT04988295), a randomized, open-label, multicenter trial in 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after receiving osimertinib. Patients were randomized (1:2:2) to receive amivantamab-vmjw with carboplatin and pemetrexed (amivantamab + CP), carboplatin and pemetrexed (CP), or amivantamab-vmjw as part of another combination regimen.

The major efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) for the comparison between amivantamab + CP and CP. Overall response rate (ORR) per BICR and overall survival (OS) were key secondary outcome measures. Median PFS was 6.3 months (95% CI: 5.6, 8.4) in the amivantamab + CP arm and 4.2 months (95% CI: 4.0, 4.4) in the CP arm (hazard ratio 0.48 [95% CI: 0.36, 0.64], p-value<0.0001). The confirmed ORR was 53% (95% CI: 44, 62) in the amivantamab + CP arm and 29% (95% CI: 23, 35) in the CP arm (p-value<0.0001).

At the prespecified second interim analysis of OS, with 85% of the deaths needed for the final analysis, there was no statistically significant difference in OS. The stratified OS hazard ratio was 0.73 (95% CI: 0.54, 0.99).

The most common adverse reactions (≥20%) were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.

The recommended amivantamab-vmjw dose is based on baseline 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 Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), and Health Canada. The application reviews are ongoing at the other regulatory agencies.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA's assessment. submission from the applicant to facilitate the FDA's assessment.

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 [email protected].