دورية أكاديمية
Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced/metastatic melanoma who have failed prior anti-PD-1 therapy.
| العنوان: | Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced/metastatic melanoma who have failed prior anti-PD-1 therapy. |
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| المؤلفون: | Kim R; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Kwon M; Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea., An M; Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea., Kim ST; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Smith SA; Oncology R&D, AstraZeneca, Cambridge, UK., Loembé AB; Oncology R&D, AstraZeneca, Cambridge, UK., Mortimer PGS; Oncology R&D, AstraZeneca, Cambridge, UK., Armenia J; Oncology R&D, AstraZeneca, Cambridge, UK., Lukashchuk N; Oncology R&D, AstraZeneca, Cambridge, UK., Shah N; Oncology R&D, AstraZeneca, Cambridge, UK., Dean E; Oncology R&D, AstraZeneca, Cambridge, UK., Park WY; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea; Geninus Inc., Seoul, Korea., Lee J; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Korea. Electronic address: jyunlee@skku.edu. |
| المصدر: | Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2022 Feb; Vol. 33 (2), pp. 193-203. Date of Electronic Publication: 2021 Oct 25. |
| نوع المنشور: | Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 9007735 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1569-8041 (Electronic) Linking ISSN: 09237534 NLM ISO Abbreviation: Ann Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : London : Elsevier Original Publication: Dordrecht ; Boston : Kluwer Academic Publishers, c1990- |
| مواضيع طبية MeSH: | Melanoma*/drug therapy , Melanoma*/genetics , Skin Neoplasms*/drug therapy, Antibodies, Monoclonal/adverse effects ; Humans ; Indoles ; Morpholines ; Pyrimidines ; Sulfonamides ; Tumor Microenvironment |
| مستخلص: | Background: Modulating the DNA damage response and repair (DDR) pathways is a promising strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related protein, which is crucial for DDR. Patients and Methods: This phase II trial evaluated ceralasertib plus durvalumab for the treatment of patients with metastatic melanoma who had failed anti-programmed cell death protein 1 therapy. Results: Among the 30 patients, we observed an overall response rate of 31.0% and a disease control rate of 63.3%. Responses were evident across patients with acral, mucosal, and cutaneous melanoma. The median duration of response was 8.8 months (range, 3.8-11.7 months). The median progression-free survival was 7.1 months (95% confidence interval, 3.6-10.6 months), and the median overall survival was 14.2 months (95% confidence interval, 9.3-19.1 months). Common adverse events were largely hematologic and manageable with dose interruptions and reductions. Exploratory biomarker analysis suggested that tumors with an immune-enriched microenvironment or alterations in the DDR pathway were more likely to respond to the study treatment. Conclusion: We conclude that ceralasertib in combination with durvalumab has promising antitumor activity among patients with metastatic melanoma who have failed anti-programmed cell death protein 1 therapy, and constitute a population with unmet needs. Competing Interests: Disclosure JL has served a consultant/advisory role for Mirati, OncXerna, Seattle Genetics, Oncologie, and AstraZeneca. ED, SS, ABL, PM, JA, NL, and NS are employees and stockholders at AstraZeneca. All other authors have declared no conflicts of interest. (Copyright © 2021. Published by Elsevier Ltd.) |
| فهرسة مساهمة: | Keywords: ataxia telangiectasia and Rad3 related protein (ATR); ceralasertib; durvalumab; immune resistance; melanoma |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Indoles) 0 (Morpholines) 0 (Pyrimidines) 0 (Sulfonamides) 28X28X9OKV (durvalumab) 85RE35306Z (ceralasertib) |
| تواريخ الأحداث: | Date Created: 20211028 Date Completed: 20220303 Latest Revision: 20220303 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.annonc.2021.10.009 |
| PMID: | 34710570 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1569-8041 |
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| DOI: | 10.1016/j.annonc.2021.10.009 |