한빛사논문
- 조회152
Hyung-Don Kim1,*, Min-Hee Ryu1,*, Young Soo Park2, Changhoon Yoo1, Sung-Joo Kim2 and Yoon-Koo Kang1
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
2Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
*Equal contribution as co-first authors.
Corresponding Author : Yoon-Koo Kang
Abstract
Purpose: In this phase Ib/II study, we aimed to evaluate the safety and efficacy of PDR001, an anti-PD-1 antibody, in combination with imatinib in patients with treatment-refractory gastrointestinal stromal tumor (GIST).
Patients and methods: Advanced GIST patients whose disease had progressed on imatinib, sunitinib, and regorafenib were enrolled. In phase Ib, the standard 3+3 dose escalation scheme was applied. PDR001 400 mg intravenously every 4 weeks plus imatinib (300 mg and 400 mg daily for dose levels I and II, respectively) was given. The primary outcome for phase II was the disease control rate (DCR) at 12 weeks. Exploratory biomarker analysis was performed based on PD-L1 immunohistochemistry, next-generation sequencing, and multiplexed immunohistochemistry.
Results: No dose-limiting toxicity was observed in the phase Ib part (n=10), and dose level 2 was selected as the recommended phase II dose. In the phase II part (n=29), there was no objective response and the DCR at 12 weeks was 37.9%, not meeting the primary efficacy endpoint. For patients in phase Ib-dose level II and phase II (n=36), the median progression-free survival (PFS) and overall survival were 2.3 and 9.5 months, respectively. The most common grade 3-4 adverse event was anemia. Exploratory biomarker analysis indicated that a higher CD8+ T cell density was associated with a favorable PFS, but to a limited degree. Tumor mutation burden and PD-L1 were not associated with better PFS.
Conclusion: In patients with treatment-refractory GIST, PDR001 in combination with imatinib was generally tolerable, but it was not effective.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-04-29)
- 국내 연구진
- 의약학 > 응용의학
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