The most common mutation in non-small cell lung cancer (NSCLC) is the EGFR mutation. Rybrevant, developed by Johnson & Johnson, is a fully human bispecific antibody against EGFR and MET with immune cell-guiding activity, which received accelerated approval from the US FDA in May 2021 for the treatment of this mutant lung cancer. Recently, the U.S. FDA approved the drug as a first-line** and converted its accelerated approval to traditional approval.
Currently, Rybrevant (amivantamab-VMJW, evantumab) has two uses:
As a single agent** in patients with locally advanced or metastatic NSCLC** who have progressed on or after platinum-based chemotherapy and have EGFR exon 20 insertion mutations.
In combination with chemotherapy (carboplatin-pemetrexed) in the first line of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations**.
Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that controls cell growth and **, and this mutation is detectable by an FDA-approved assay.
Notably, Rybrevant in combination with chemotherapy is the first FDA-approved treatment for first-line NSCLC patients with EGFR exon 20 insertion mutations.
In addition, based on the results of the Papillon study, the NCCN Guidelines updated its clinical practice guidelines to include Rybrevant in combination with chemotherapy as the preferred first-line approach for patients with NSCLC with EGFR exon 20 insertion mutations** into Category 1 recommendations.
The approval was based on data from the confirmatory Phase 3 Papillon trial (NCT04538664), which included 308 patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, Eastern Cooperative Oncology Group performance status (PS) 1, and adequate organ and bone marrow function.
Study participants were randomly assigned to receive amivantamab in combination with 'carboplatin + pemetrexed' (n = 153) or 'carboplatin + pemetrexed' (n = 155). The primary endpoint is progression-free survival (PFS).
The results showed a statistically significant improvement in PFS in patients who received amivantamab in combination with carboplatin + pemetrexed** compared to patients who received carboplatin + pemetrexed** (hazard ratio, 0.).40[95%ci，0.30-0.53]；p<0.0001)。The median PFS was 114 months (95% CI, 9.)8-13.7) and 67 months (95% CI, 5.)6-7.3）。
The overall response rate in amivantamab plus carboplatin + pemetrexed was 67 percent (95% CI, 59-75), with a complete response of 4 percent and a partial response of 63 percent; The overall response rate in the carboplatin + pemetrexed arm was 36 percent (95% CI, 29-44), with 1 percent achieving complete response and 36 percent partial response. The median duration of response was 101 month (95% CI, 8.)5-13.9) and 56 months (95% CI, 4.)4-6.9）。
At the time of analysis, overall survival results were immature (the researchers did not have enough data to calculate the average), but no harmful trends were observed. Forty-eight percent of patients (n = 75) switched from 'carboplatin + pemetrexed' to amivantamab monotherapy after confirmed disease progression**.
The most common adverse reactions were rash, nail toxicity, stomatitis, infusion-related reactions, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting.
Reference**: Rybrevant (amivantamab-VMJW) in combination with chemotherapy is the first FDA approved therapy for first-line treatment of patients with non-small cell lung cancer with EGFR EXON 20 Insertion mutations', press release. johnson & johnson；Released on March 1, 2024.
Note: The purpose of this article is to introduce medical and health research, and does not make any basis for medication.