دورية أكاديمية
Pembrolizumab plus dinaciclib in patients with hematologic malignancies: the phase 1b KEYNOTE-155 study
العنوان: | Pembrolizumab plus dinaciclib in patients with hematologic malignancies: the phase 1b KEYNOTE-155 study |
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المؤلفون: | Gregory, Gareth Peter, Kumar, Shaji K, Wang, Ding, Mahadevan, Daruka, Walker, Patricia A, Wagner-Johnston, Nina D, Escobar, Carolina, Bannerji, Rajat, Bhutani, Divava, Chang, Julie E, Hernandez-Ilizaliturri, Francisco J, Klein, Andreas, Pagel, John M, Rybka, Witold, Yee, Andrew J, Mohrbacher, Anne, Huang, Mo, Farooqui, Mohammed Z. H., Marinello, Patricia, Quach, Hang |
المصدر: | Hematology/Oncology Articles |
بيانات النشر: | Henry Ford Health Scholarly Commons |
سنة النشر: | 2021 |
المجموعة: | Henry Ford Health System Scholarly Commons |
الوصف: | Preclinical data demonstrated that combining an anti-programmed cell death 1 (PD-1) inhibitor with a CDK9 inhibitor provided enhanced antitumor activity with no significant toxicities, suggesting this combination may be a potential therapeutic option. The multicohort, phase 1 KEYNOTE-155 study evaluated the safety and antitumor activity of the PD-1 inhibitor pembrolizumab plus the CDK9 inhibitor dinaciclib in patients with relapsed or refractory (rr) chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Patients enrolled were ≥18 years of age with a confirmed diagnosis of CLL, DLBCL, or MM. The study included 2 phases: a dose-evaluation phase to determine dose-limiting toxicities and a signal-detection phase. Patients received pembrolizumab 200 mg every 3 weeks plus dinaciclib 7 mg/m2 on day 1 and 10 mg/m2 on day 8 of cycle 1 and 14 mg/m2 on days 1 and 8 of cycles 2 and later. Primary endpoint was safety, and a key secondary endpoint was objective response rate (ORR), Seventy-two patients were enrolled and received ≥1 dose of study treatment (CLL, n = 17; DLBCL, n = 38; MM, n = 17). Pembrolizumab plus dinaciclib was generally well tolerated and produced no unexpected toxicities. The ORRs were 29.4% (5/17, rrCLL), 21.1% (8/38, rrDLBCL), and 0% (0/17, rrMM), respectively. At data cutoff, all 72 patients had discontinued treatment, 38 (52.8%) because of progressive disease. These findings demonstrate activity with combination pembrolizumab plus dinaciclib and suggest that a careful and comprehensive approach to explore anti-PD-1 and CDK9 inhibitor combinations is warranted. Clinical trial registration: ClinicalTrials.gov, NCT02684617. |
نوع الوثيقة: | text |
اللغة: | unknown |
العلاقة: | https://scholarlycommons.henryford.com/hematologyoncology_articles/220Test; https://libkey.io/34972202Test |
الإتاحة: | https://scholarlycommons.henryford.com/hematologyoncology_articles/220Test https://libkey.io/34972202Test |
رقم الانضمام: | edsbas.DEBE80E5 |
قاعدة البيانات: | BASE |
الوصف غير متاح. |