FDA Approves Amivantamab/Chemo in EGFR Exon 20+ NSCLC

The FDA based its approval on findings from the phase 3 PAPILLON trial (NCT04538664).

The News

The FDA has granted approval to amivantamab-vmjw (Rybrevant) in combination with carboplatin and pemetrexed as frontline therapy for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations as detected with an FDA-approved test, according to a press release from the FDA.¹

The FDA also granted regular approval to amivantamab as a treatment 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.

Supporting Data

The regulatory agency based its approval on findings from the phase 3 PAPILLON trial (NCT04538664).

Amivantamab plus chemotherapy produced a median progression-free survival (PFS) of 11.4 months (95% CI, 9.8-13.7) compared with 6.7 months (95% CI, 5.6-7.3) in those who received chemotherapy alone (HR, 0.40; 95% CI, 0.30-0.53; P <.0001).

Investigators observed no detriment to overall survival (OS) with the experimental combination, although data were immature at the time of the final analysis as 44% of pre-specified deaths were reported. According to data published in The New England Journal of Medicine, the median OS was not evaluable (NE; 95% CI, NE-NE) in the amivantamab combination arm vs 24.4 months (95% CI, 22.1-NE) in the chemotherapy alone arm.² In each respective arm, the OS rates were 74% vs 72% at 18 months and 68% vs 54% at 24 months.

Safety Information

The most common adverse effects (AEs) in the PAPILLON trial included rash, nail toxicity, stomatitis, infusion-related reactions, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting.

PAPILLON Design

The open-label, multicenter PAPILLON trial included 308 patients who were randomly assigned 1:1 to receive amivantamab plus chemotherapy (n = 153) or chemotherapy alone (n = 155). Investigators administered amivantamab at 1400 mg (1750 mg if 80 kg or higher) for the first 4 weeks followed by 1750 mg (2100 mg if 80 kg or higher) every 3 weeks starting at week 7. Chemotherapy consisted of carboplatin at area under the curve of 5 for the first 4 cycles plus pemetrexed at 500 mg/m² until progressive disease.

The trial’s primary end point was PFS based on blinded independent central review (BICR). OS was a key secondary end point.

The FDA previously accepted a supplemental biologics license application for amivantamab plus chemotherapy for patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations in August 2023.³ The FDA granted accelerated approval to amivantamab and chemotherapy for the aforementioned population following progression on platinum-based chemotherapy in 2021.⁴

References

1. FDA approves amivantamab-vmjw for EGFR exon 20 insertion-mutated non-small cell lung cancer indications. News release. FDA. March 1, 2024. Accessed March 1, 2024. https://tinyurl.com/msw4u5yk
2. Zhou C, Tang K, Cho BC, et al. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N Engl J Med. 2023;389(22):2039-2051. doi:10.1056/NEJMoa2306441
3. Janssen submits supplemental biologics license application to the U.S. Food and Drug Administration seeking approval of RYBREVANT® (amivantamab-vmjw) in combination with chemotherapy for the first-line treatment of patients with locally advanced or metastatic EGFR exon 20 insertion mutation-positive non-small cell lung cancer. News release. Janssen Pharmaceuticals. August 25, 2023. Accessed March 1, 2024. https://shorturl.at/lAPU8
4. FDA grants accelerated approval to amivantamab-vmjw for metastatic non-small cell lung cancer. News release. FDA. May 21, 2021. Accessed March 1, 2024. https://tinyurl.com/mr29uxza