دورية أكاديمية
Clinical and Biomarker Analysis of a Phase I/II Study of PDR001 Plus Imatinib for Advanced Treatment-Refractory Gastrointestinal Stromal Tumors.
| العنوان: | Clinical and Biomarker Analysis of a Phase I/II Study of PDR001 Plus Imatinib for Advanced Treatment-Refractory Gastrointestinal Stromal Tumors. |
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| المؤلفون: | Kim HD; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Ryu MH; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Park YS; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Yoo C; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kim SJ; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kang YK; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Jul 01; Vol. 30 (13), pp. 2743-2750. |
| نوع المنشور: | Journal Article; Clinical Trial, Phase II; Clinical Trial, Phase I |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Gastrointestinal Stromal Tumors*/drug therapy , Gastrointestinal Stromal Tumors*/pathology , Gastrointestinal Stromal Tumors*/genetics , Imatinib Mesylate*/administration & dosage , Imatinib Mesylate*/adverse effects , Imatinib Mesylate*/therapeutic use , Biomarkers, Tumor* , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Antineoplastic Combined Chemotherapy Protocols*/adverse effects, Humans ; Female ; Male ; Middle Aged ; Aged ; Adult ; Gastrointestinal Neoplasms/drug therapy ; Gastrointestinal Neoplasms/pathology ; Drug Resistance, Neoplasm |
| مستخلص: | Purpose: In this phase Ib/II study, we aimed to evaluate the safety and efficacy of PDR001, an anti-PD1 antibody, in combination with imatinib in patients with treatment-refractory gastrointestinal stromal tumor (GIST). Patients and Methods: Patients with advanced GIST whose disease had progressed on imatinib, sunitinib, and regorafenib were enrolled. In phase Ib, the standard 3 + 3 dose escalation scheme was applied. Intravenous administration of PDR001 at 400 mg for every 4 weeks plus imatinib (300 and 400 mg daily for dose levels I and II, respectively) was given. The primary outcome for phase II was the disease control rate at 12 weeks. Exploratory biomarker analysis was performed based on PDL1 IHC, next-generation sequencing, and multiplexed IHC. Results: No dose-limiting toxicity was observed in the phase Ib part (n = 10), and dose level II was selected as the recommended phase II dose. In the phase II part (n = 29), there was no objective response, and the disease control rate 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 to 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 mutational burden and PDL1 were not associated with better PFS. Conclusions: In patients with treatment-refractory GIST, PDR001 in combination with imatinib was generally tolerable, but it was not effective. (©2024 American Association for Cancer Research.) |
| معلومات مُعتمدة: | 2021IP0062 Asan Institute for Life Sciences, Asan Medical Center |
| المشرفين على المادة: | 8A1O1M485B (Imatinib Mesylate) 0 (Biomarkers, Tumor) |
| تواريخ الأحداث: | Date Created: 20240425 Date Completed: 20240701 Latest Revision: 20240701 |
| رمز التحديث: | 20240701 |
| DOI: | 10.1158/1078-0432.CCR-23-4065 |
| PMID: | 38662455 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-23-4065 |