دورية أكاديمية
Phase I Study of Single-Agent Anti-Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates
| العنوان: | Phase I Study of Single-Agent Anti-Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates |
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| المؤلفون: | Brahmer, Julie R, Drake, Charles G, Wollner, Ira, Powderly, John D, Picus, Joel, Sharfman, William H, Stankevich, Elizabeth, Pons, Alice, Salay, Theresa M, McMiller, Tracee L, Gilson, Marta M, Wang, Changyu, Selby, Mark, Taube, Janis M, Anders, Robert, Chen, Lieping, Korman, Alan J, Pardoll, Drew M, Lowy, Israel, Topalian, Suzanne L |
| المصدر: | Hematology/Oncology Articles |
| بيانات النشر: | Henry Ford Health Scholarly Commons |
| سنة النشر: | 2023 |
| المجموعة: | Henry Ford Health System Scholarly Commons |
| الوصف: | PURPOSE: Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. PATIENTS AND METHODS: Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non-small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti-PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy. RESULTS: Anti-PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti-PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells ≥ 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment. CONCLUSION: Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted. |
| نوع الوثيقة: | text |
| اللغة: | unknown |
| العلاقة: | https://scholarlycommons.henryford.com/hematologyoncology_articles/285Test; https://libkey.io/36706735Test |
| الإتاحة: | https://scholarlycommons.henryford.com/hematologyoncology_articles/285Test https://libkey.io/36706735Test |
| رقم الانضمام: | edsbas.88E42763 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |