Dr Leighl on Amivantamab in Advanced NSCLC With MET Exon 14 Skipping Mutations

Natasha B. Leighl, BSc, MMSc, MD, clinician investigator, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, discusses efficacy findings with the EGFR/MET inhibitor amivantamab-vmjw (Rybrevant) in patients with advanced non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations.

At the 2023 IASLC World Conference on Lung Cancer, Leighl presented updated findings from the ongoing phase 1 CHRYSALIS trial (NCT02609776) that investigated the efficacy of amivantamab monotherapy in patients with advanced NSCLC with MET exon 14 skipping mutations whose disease had progressed on or who had declined the current regional standard-of-care therapy.

At a median follow-up of 10.0 months, 97 patients had received amivantamab in this trial. Of these patients, 16, 28, and 53 were treatment naïve, had prior treatment but no prior MET inhibitor, and a prior MET inhibitor, respectively. Common MET inhibitors used in prior lines of therapy included capmatinib (Tabrecta) and tepotinib (Tepmetko), Leighl says.

The overall response rate (ORR) in the entire population was 33%, with a median duration of response (DOR) of 11.2 months (95% CI, 5.3-19.0). Fifteenpatients had a DOR of at least 6 months, and 12 patients were still receiving the study treatment at the data cutoff date. Among the 49 patients who achieved stable disease, 48 experienced reductions in tumor size. In the cohorts of patients with treatment-naïve, no prior MET inhibition, and prior MET inhibition, the ORRs were 50%, 46%, and 21%, respectively. In addition, the clinical benefit rate (CBR) in the overall population was 70% (95% CI, 60%-79%), and the CBRs in the treatment naïve, no prior MET inhibition, and prior MET inhibition cohorts were 88% (95% CI, 62%-98%), 64% (95% CI, 44%-81%), and 68% (95% CI, 54%-80%), respectively. Median progression-free survival and overall survival were 5.4 months (95% CI, 4.3-7.0) and 15.8 months (95% CI, 13.1-21.8), respectively.

The most common treatment-emergent adverse effects (TEAEs) were rash, infusion-related reactions, and paronychia. Furthermore, 42% of patients experienced TEAEs of grade 3 or higher, and 20% of grade 3 or higher TEAEs were reported as treatment related.