Immunologic and tumor responses of pegilodecakin with 5-FU/LV and oxaliplatin (FOLFOX) in pancreatic ductal adenocarcinoma (PDAC)
| العنوان: | Immunologic and tumor responses of pegilodecakin with 5-FU/LV and oxaliplatin (FOLFOX) in pancreatic ductal adenocarcinoma (PDAC) |
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| المؤلفون: | Sujata Rao, Rakesh Verma, Todd M. Bauer, Aung Naing, J. Leveque, Raid Aljumaily, Zev A. Wainberg, Johanna C. Bendell, J. Randolph Hecht, Gerald Steven Falchook, Martin Oft, Annie Hung, Karen A. Autio, Shubham Pant, Jeffrey R. Infante, Navneet Ratti, Deborah J. Wong, Manish R. Patel, Kyriakos P. Papadopoulos, Peter VanVlasselaer, Milind Javle |
| المصدر: | Investigational new drugs, vol 39, iss 1 Invest New Drugs |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Organoplatinum Compounds, Metastatic pancreatic adenocarcinoma, Leucovorin, Phases of clinical research, Kaplan-Meier Estimate, Polyethylene Glycols, 0302 clinical medicine, FOLFOX, Antineoplastic Combined Chemotherapy Protocols, Pharmacology (medical), 6.2 Cellular and gene therapies, Cancer, education.field_of_study, Pharmacology and Pharmaceutical Sciences, Middle Aged, Progression-Free Survival, Interleukin-10, Tolerability, Pancreatic Ductal, 6.1 Pharmaceuticals, 030220 oncology & carcinogenesis, IL-10, Fluorouracil, Pegilodecakin, Drug, Carcinoma, Pancreatic Ductal, medicine.drug, Adult, medicine.medical_specialty, Clinical Trials and Supportive Activities, Population, Phase 1, Article, Dose-Response Relationship, Pancreatic Cancer, 03 medical and health sciences, Rare Diseases, Clinical Research, Internal medicine, medicine, Humans, Oncology & Carcinogenesis, Pegylated IL-10, Adverse effect, education, Response Evaluation Criteria in Solid Tumors, Neoplasm Staging, Aged, Pharmacology, Dose-Response Relationship, Drug, business.industry, Carcinoma, Evaluation of treatments and therapeutic interventions, digestive system diseases, Oxaliplatin, Pancreatic Neoplasms, Regimen, 030104 developmental biology, Tumor progression, Digestive Diseases, business |
| الوصف: | Background Treatment options for pancreatic ductal adenocarcinoma (PDAC) are limited and checkpoint blockade inhibitors have been disappointing in this disease. Pegilodecakin has demonstrated single agent anti-tumor activity in immune-sensitive tumors. Phase 1 and preclinical data indicate synergy of pegilodecakin with 5-FU and platins. We assessed the safety and activity of pegilodecakin+FOLFOX in patients with PDAC. Methods IVY (NCT02009449) was an open-label phase 1b trial in the United States. Here we report on all enrolled patients from cohort C. Heavily pretreated patients were treated with pegilodecakin (self-administered subcutaneously daily at 2.5, 5, or 10μg/kg) + 5-flurouracil/leucovorin/oxaliplatin (FOLFOX), dosed per manufacturers prescribing information, until tumor progression. Eligible patients had measurable disease per immune-related response criteria (irRC), were ≥ 18years of age, and had ECOG performance status of 0 or 1. Patients were evaluated for primary(safety) and secondary (tumor response per irRC) endpoints. Results From 5 August 2014-12 July 2016, 39 patients enrolled in cohort C. All patients were evaluable for safety. In this advanced population, regimen had manageable toxicities with no immune-related adverse events (irAEs) greater than grade 1. The most common grade 3/4/5 TEAEs were thrombocytopenia (21[53.8%] of 39) and anemia (17[43.6%] of 39). In evaluable PDAC patients, the best overall response of pegilodecakin+FOLFOX was 3(14%) with CRs in 2(9%) patients. Conclusions Pegilodecakin+FOLFOX had an acceptable tolerability profile in PDAC, with no substantial irAEs seen, and promising efficacy with the combination yielding a 2-year OS of 24% (95% CI 10-42). These data led to the phase 3 study with pegilodecakin+FOLFOX as second-line therapy of PDAC (SEQUOIA). |
| وصف الملف: | application/pdf |
| تدمد: | 1573-0646 0167-6997 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d69d0ddd9f3551a8ca0a4d0daab7d846 https://doi.org/10.1007/s10637-020-01000-6 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d69d0ddd9f3551a8ca0a4d0daab7d846 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15730646 01676997 |
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