Zipalertinib Demonstrated Promising Anti-Tumor Activity Among Patients With EGFR-Mutated Non-Small Cell Lung Cancer

According to results from the phase 2b REZILIENT1 study, zipalertinib, a novel irreversible and selective EGFR tyrosine kinase inhibitor, demonstrated promising efficacy among patients with EGFR exon 20 insertion mutations in non-small cell lung cancer (NSCLC) who experienced disease progression after treatment with amivantamab. 

These results will be presented by Antonio Passaro, MD, PhD, European Institute of Oncology, Milan, Italy, at the 2024 European Society for Medical Oncology (ESMO) Congress. 

In this open-label trial, 45 patients with NSCLC who experienced disease progression after at least 1 prior line of amivantamab were enrolled to receive 100 mg of twice daily zipalertinib. The primary end point was safety. Key secondary end points included response, objective response rate (ORR), disease control rate, duration of response, and progression-free survival (PFS).

The most frequent treatment-related adverse events, occurring in ≥ 10% of patients, were rash (38%), paronychia (36%), anemia (24%), dry skin (20%), dermatitis acneiform (16%), nausea (16%), and stomatitis (11%). Grade 3 treatment-related adverse events were experienced by 14 patients and most frequently included anemia (n = 4), rash (n = 3), and pneumonitis/interstitial lung disease (n = 3). No grade 4/5 events were reported. Three patients underwent dose reductions or treatment discontinuation due to treatment-related adverse events. 

At the data cut-off date, 30 patients were evaluable for response of which 1 had complete response, 11 had partial responses, and 15 achieved stable disease. The ORR was 40% and the disease control rate was 90%. Median duration of response was not yet estimable and median PFS was 9.7 months. 

“In this amivantamab resistant setting, zipalertinib demonstrated promising efficacy, similar to [patients] that progressed after platinum-based chemotherapy alone and had a manageable safety profile,” concluded Dr Passaro et al. 

Source: 

Passaro A, Yu HA, Nguyen D, et al. Safety and anti-tumour activity of zipalertinib in NSCLC patients (pts) with EGFR exon 20 insertion (ex20ins) mutations who received prior amivantamab. Presented at the 2024 ESMO Congress; September 13-17, 2024. Barcelona, Spain. Abstract 1254MO