한빛사 논문
R. Kim1,∗, M. Kwon2,∗, M. An3,∗, S.T. Kim1, S.A. Smith4, A.B. Loembé4, P.G.S. Mortimer4, J. Armenia4, N. Lukashchuk4, N. Shah4, E. Dean4, W.-Y. Park5,6, J. Lee1,7
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea
3Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea
4Oncology R&D, AstraZeneca, Cambridge, United Kingdom
5Samsung Genome Institute, Samsung Medical Center, Seoul, Korea
6Geninus Inc., Seoul, Korea
7Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Korea
*R. Kim, M. Kwon, and M. An contributed equally to this study as first authors.
CORRESPONDING AUTHOR : Dr Jeeyun Lee, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea, Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, Korea
Abstract
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 (MM) who had failed anti-PD1 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). The median progression-free survival was 7.1 months (95% confidence interval, 3.6–10.6) and the median overall survival was 14.2 months (95% confidence interval, 9.3–19.1). 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 anti-tumor activity among patients with MM who have failed anti-PD1 therapy, and constitute a population with unmet needs.
KEYWORDS : Ataxia telangiectasia and Rad3 related protein (ATR), melanoma, durvalumab, ceralasertib, immune resistance
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