Zofia Piotrowska, Antonio Passaro, Danny Nguyen, Gerrina Ruiter, Ross A Soo, Victor Ho-Fun Lee, Vamsidhar Velcheti, Daniel Shao-Weng Tan, Se-Hoon Lee, Se Hyun Kim, John Wrangle, James Chih-Hsin Yang, Haruko Daga, Oscar J Juan Vidal, Alexander I Spira, Gonzalo Fernandez-Hinojal, Sang-We Kim, Shigeki Umemura, Mariano Provencio Pulla, Erika K Keeton, Zhihui Sunny Yang, Shengting Li, Zhiying Cindy Xu, Jeffrey A Jones, Helena Alexandra Yu
{"title":"Zipalertinib在EGFR外显子20插入阳性NSCLC患者中的应用","authors":"Zofia Piotrowska, Antonio Passaro, Danny Nguyen, Gerrina Ruiter, Ross A Soo, Victor Ho-Fun Lee, Vamsidhar Velcheti, Daniel Shao-Weng Tan, Se-Hoon Lee, Se Hyun Kim, John Wrangle, James Chih-Hsin Yang, Haruko Daga, Oscar J Juan Vidal, Alexander I Spira, Gonzalo Fernandez-Hinojal, Sang-We Kim, Shigeki Umemura, Mariano Provencio Pulla, Erika K Keeton, Zhihui Sunny Yang, Shengting Li, Zhiying Cindy Xu, Jeffrey A Jones, Helena Alexandra Yu","doi":"10.1200/JCO-25-00763","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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 <i>EGFR</i> exon 20 insertion (ex20ins) mutations.</p><p><strong>Methods: </strong>REZILIENT1 (ClinicalTrials.gov identifier: NCT04036682) is a phase I/II open-label trial enrolling patients with locally advanced or metastatic <i>EGFR</i> 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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with <i>EGFR</i> ex20ins-mutant NSCLC who received prior platinum-based chemotherapy with or without amivantamab.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500763"},"PeriodicalIF":42.1000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Zofia Piotrowska, Antonio Passaro, Danny Nguyen, Gerrina Ruiter, Ross A Soo, Victor Ho-Fun Lee, Vamsidhar Velcheti, Daniel Shao-Weng Tan, Se-Hoon Lee, Se Hyun Kim, John Wrangle, James Chih-Hsin Yang, Haruko Daga, Oscar J Juan Vidal, Alexander I Spira, Gonzalo Fernandez-Hinojal, Sang-We Kim, Shigeki Umemura, Mariano Provencio Pulla, Erika K Keeton, Zhihui Sunny Yang, Shengting Li, Zhiying Cindy Xu, Jeffrey A Jones, Helena Alexandra Yu\",\"doi\":\"10.1200/JCO-25-00763\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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 <i>EGFR</i> exon 20 insertion (ex20ins) mutations.</p><p><strong>Methods: </strong>REZILIENT1 (ClinicalTrials.gov identifier: NCT04036682) is a phase I/II open-label trial enrolling patients with locally advanced or metastatic <i>EGFR</i> 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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with <i>EGFR</i> ex20ins-mutant NSCLC who received prior platinum-based chemotherapy with or without amivantamab.</p>\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":\" \",\"pages\":\"JCO2500763\"},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/JCO-25-00763\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO-25-00763","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.
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The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
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