Biomarker Analysis Predicts Post-Osimertinib Response in EGFR+ NSCLC

Benjamin Besse, MD, PhD, professor of medical oncology at Université Paris-Saclay and head of clinical research at Gustave Roussy, discusses the biomarker analysis of the phase 1/1b CHRYSALIS-2 (NCT04077463) study of amivantamab (Rybrevant) and lazertinib (Leclaza) in patients with EGFR-mutated non–small cell lung cancer (NSCLC).

The trial enrolled patients who had previously received osimertinib (Tagrisso) for EGFR-mutated NSCLC. Besse says that 77 patients had a biopsy after exposure to osimertinib and a signature of MET protein expression by immunohistochemistry was associated with EGFR inhibitor resistance. Patients with 3+ staining in at least 25% of tumor cells were considered MET-positive, which comprised 36% of the population.

In the MET-positive patients, the overall response rate (ORR) to lazertinib/amivantamab was 61% and the median progression-free survival (PFS) was 12.2 months, whereas in the MET-negative patients, the ORR was 14% and the median PFS was 4.2 months.

These results show a divide between outcomes of patients with high and low MET expression with this combination. According to Besse, 2 new cohorts will enroll patients to confirm these results.

TRANSCRIPTION:

0:08 | The goal was to train a signature on the tissue to find what are the patients that benefited the most with this combination. In this cohort, all the patients had a mandatory biopsy before receiving the combination. After the exposure of the osimertinib, 77 patients got a biopsy and in this tissue, we trained signatures. The signature that was the most positive was the expression by the tumor cells of the protein MET on the surface of the cell. It's a very simple test. It's an immunohistochemistry, it's simple and available everywhere. The threshold for positivity was a 3+ staining in at least 25% of the cells.

1:00 | We defined a MET-positive group and the MET-negative group. Thirty-six percent of the patients were considered MET-positive so in the MET-positive group. In this population, the response rate to lazertinib plus amivantamab was 61% and the median PFS [was] 12.2 months. When MET was negative, the response rate was 14% and the median PFS was 4.2 months. This biomarker very simple seems to really discriminate 2 populations: 1 with a high response and high benefit to the combination post-osimertinib. It needs to be confirmed, so 2 new cohorts will open and enroll patients to confirm this data.