Zipalertinib in Patients With Epidermal Growth Factor Receptor Exon 20 Insertion-Positive Non–Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab
Зипалертиниб у пациентов с немелкоклеточным раком легкого с мутациями вставки в экзоне 20 рецептора эпидермального фактора роста, ранее получавших платиновую химиотерапию с амивантамабом или без него
2025-06-01
SCID: 54.1/6qpzcvhw
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EGFR exon 20 insertion (ex20ins)duration of response (DOR)non–small cell lung cancer (NSCLC)objective response rate (ORR)zipalertinib
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Abstract (AI)
PURPOSE To evaluate the safety and efficacy of zipalertinib, an irreversible epidermal growth factor receptor (EGFR) inhibitor, in pretreated patients with non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (ex20ins) mutations. METHODS REZILIENT1 (ClinicalTrials.gov identifier: NCT04036682 ) is a phase I/II open-label trial enrolling patients with locally advanced or metastatic EGFR ex20ins-mutant NSCLC previously treated with platinum-based chemotherapy with/without ex20ins-targeted therapies. Asymptomatic, treated and untreated stable CNS metastases are permitted. We report data from patients treated with zipalertinib 100 mg twice daily. The primary end points are objective response rate (ORR) and duration of response (DOR) by independent central review. RESULTS At data cutoff (December 10, 2024), 244 patients had received treatment with zipalertinib 100 mg twice daily. The primary efficacy population (8 months' follow-up) comprised patients who had received prior platinum-based chemotherapy without ex20ins-targeted therapy (125 patients), with amivantamab only (30 patients), or with amivantamab and other ex20ins-targeted therapy (21 patients). The confirmed ORR was 35.2% (95% CI, 28.2 to 42.8); median DOR was 8.8 months (95% CI, 8.3 to 12.7). Among patients who received prior platinum-based chemotherapy without ex20ins-targeted therapy, amivantamab only, or amivantamab and other ex20ins-targeted therapy, the confirmed ORR was 40%, 30%, and 14.3%, and median DOR was 8.8, 14.7, and 4.2 months, respectively. Among 68 patients with CNS metastases, the ORR was 30.9%. The most common grade ≥3 treatment-related adverse events were anemia (7%), pneumonitis and rash (2.5% each), and diarrhea, ALT increased, and platelet count decreased (2% each). CONCLUSION Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with EGFR ex20ins-mutant NSCLC who received prior platinum-based chemotherapy with or without amivantamab.
Key Findings
1
Among 68 patients with CNS metastases, zipalertinib achieved an ORR of 30.9%; most common grade ≥3 treatment-related adverse events included anemia (7%), pneumonitis and rash (2.5% each).
2
Median DOR by prior therapy was 8.8 months (platinum only), 14.7 months (amivantamab only), and 4.2 months (amivantamab plus other targeted therapy).
3
Median duration of response (DOR) for the overall population was 8.8 months (95% CI, 8.3 to 12.7).
4
ORR varied by prior therapy: 40% in patients with prior platinum chemotherapy only, 30% with prior amivantamab only, and 14.3% with prior amivantamab plus other ex20ins-targeted therapy.
5
Zipalertinib 100 mg twice daily produced a confirmed objective response rate (ORR) of 35.2% (95% CI, 28.2 to 42.8) in EGFR exon 20 insertion–positive NSCLC previously treated with platinum chemotherapy.
Research Object
Patients with EGFR exon 20 insertion–positive non–small cell lung cancer previously treated with platinum-based chemotherapy with or without amivantamab
Research Subject
Efficacy and safety of zipalertinib 100 mg twice daily, measured by objective response rate and duration of response (primary endpoints) and treatment-related adverse events in this patient population
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2025-06-01
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