FDA Approves Amivantamab/Chemo in Advanced EGFR Exon20Ins Mut+ NSCLC

• Amivantamab-vmjw (Rybrevant) is now an FDA-approved treatment option for patients with EGFR exon 20 insertion mutation-positive non-small cell lung cancer (NSCLC).
• Findings from the phase 3 PAPILLON trial (NCT04538664) support this regulatory decision.
• In the trial, amivantamab with carboplatin and pemetrexed showed a statistically significant improvement in progression-free survival (PFS) vs carboplatin and pemetrexed.

The FDA has approved amivantamab with carboplatin and pemetrexed as a first-line treatment in patients with EGFR exon 20 insertion mutation-positive NSCLC.¹

This approval is supported by findings from the phase 3 PAPILLON study which showed the combination of amivantamab, carboplatin, and pemetrexed to demonstrate a PFS of 11.4 months (95% CI, 9.8-13.7) vs 6.7 months (95% CI, 5.6-7.3) for carboplatin and pemetrexed (HR, .40; 95% CI, 0.30-0.53; P<.0001). For the secondary end point of overall survival (OS), findings were immature at the time of the current analysis. Further, 44% of pre-specified deaths for the final analysis were and there was no no trend towards a detriment seen.

For safety, the most common adverse events (AEs; ≥20%) observed with the combination included rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting.

“Bringing amivantamab upfront with chemotherapy for EGFR exon 20 insertions may change the standard-of-care,” Jonathan W. Riess, MD, medical director of thoracic oncology, University of California, Davis Comprehensive Cancer Center, previously told Targeted Oncology, in an interview.

In addition, the FDA granted traditional approval to amivantamabfor the treatment of 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.

About the PAPILLON Trial

The phase 3 PAPILLON trial randomized 308 patients with EGFR exon 20 insertion mutations to receive either amivantamab with or without carboplatin and pemetrexed. The primary end point was PFS assessed by blinded independent central review. OS was the key secondary end point.¹ Other secondary end points included included objective response rate, duration of response, PFS after first subsequent therapy, time to symptomatic progression, intracranial PFS, and incidence and severity of AEs.²

Patients were eligible to enroll in the trial if they had histologically or cytologically confirmed locally advanced or metastatic NSCLC with primary EGFR exon 20 insertion activating mutation, had an ECOG performance status of 0 or 1, and agreed to genetic characterization of tumor status. Women of childbearing potential must have had a negative pregnancy test within 72 hours of the first study dose and agree to further serum or urine pregnancy tests during the study.

Patients were ineligible for enrollment if they had evidence of synchronous NSCLC disease, untreated brain metastases, history of spinal cord compression, history of interstitial lung disease, contraindication to carboplatin or pemetrexed, or a hypersensitivity to vitamin B12 or folic acid.

According to the press release from the FDA, the recommended dose of amivantamab is based on body weight.¹

REFERENCES:

1. FDA approvesamivantamab-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/2p9v9632

2. A study of combination amivantamab and carboplatin-pemetrexed therapy, compared with carboplatin-pemetrexed, in participants with advanced or metastatic non-small cell lung cancer characterized by epidermal growth factor receptor (EGFR) exon 20 insertions (PAPILLON). ClinicalTrials.gov. Updated February 28, 2024. Accessed March 1, 2024. https://www.clinicaltrials.gov/study/NCT04538664