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dc.contributor.authorRibrag, Vincent
dc.contributor.authorLee, Seung Tae
dc.contributor.authorRizzieri, David
dc.contributor.authorDyer, Martin J S
dc.contributor.authorFayad, Luis
dc.contributor.authorKurzrock, Razelle
dc.contributor.authorAndritsos, Leslie
dc.contributor.authorBouabdallah, Reda
dc.contributor.authorHayat, Amjad
dc.contributor.authorBacon, Larry
dc.contributor.authorJiang, Yu
dc.contributor.authorMiah, Kowser
dc.contributor.authorDelafont, Bruno
dc.contributor.authorHamid, Oday
dc.contributor.authorAnyanwu, Stephanie
dc.contributor.authorMartinez, Pablo
dc.contributor.authorHess, Brian
dc.date.accessioned2021-03-05T15:59:33Z
dc.date.available2021-03-05T15:59:33Z
dc.date.issued2020-12-17
dc.identifier.urihttp://hdl.handle.net/10713/14839
dc.description.abstractBackground: Despite recent advances, outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) remain poor. Immune checkpoint inhibitors have shown limited efficacy in this setting, but combinations with novel agents may enhance benefit. Combination therapy with durvalumab, an anti–programmed death ligand 1 (PD-L1) antibody, and danvatirsen (AZD9150; an antisense oligonucleotide inhibiting signal transducer and activator of transcription 3 [STAT3]) or tremelimumab (an anti–cytotoxic T-lymphocyte–associated antigen 4 [CTLA-4] antibody) may augment endogenous antitumor activity. Patients and Methods: In this phase 1b dose escalation and dose expansion study, we evaluated durvalumab 20 mg/kg every 4 weeks plus either tremelimumab 1 mg/kg every 4 weeks or danvatirsen 2 or 3 mg/kg (administered on days 1, 3, 5, 8, 15, and 22, then every week). Treatment continued until disease progression. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics, and immunogenicity. Results: As of April 4, 2019, 32 patients were enrolled and treated, receiving a median of 2 prior lines of systemic therapy. Treatment-related adverse events occurred in 21 patients (65.6%), most commonly alanine aminotransferase/aspartate aminotransferase increased (grade 1-3), anemia (grade 1-3), and fatigue (grade 1). The overall objective response rate was 6.3%, with 2 partial responses. Median time to response was 11.0 weeks (range, 7.7-14.3 weeks). Median progression-free survival was 7.4 weeks (range, 0.1-31.4 weeks), and median overall survival was 28.0 weeks (range, 1.9-115.4 weeks). Conclusion: The primary endpoint was met, with durvalumab plus tremelimumab/danvatirsen generally well tolerated in patients with relapsed/refractory DLBCL; however, antitumor activity was limited. Combination therapy may enhance outcomes with immune checkpoint inhibitors in patients with relapsed/refractory diffuse large B-cell lymphoma. In this dose expansion/dose escalation study in 32 patients, durvalumab combined with tremelimumab or the STAT3 inhibitor danvatirsen was generally well tolerated but had limited efficacy. Evaluation in preselected cases may clarify the role of anti-STAT3 agents in this setting. © 2020 The Authorsen_US
dc.description.urihttps://doi.org/10.1016/j.clml.2020.12.012en_US
dc.language.isoenen_US
dc.publisherElsevier Ltd.en_US
dc.relation.ispartofClinical lymphoma, Myeloma & Leukemiaen_US
dc.rightsCopyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.en_US
dc.subjectDLBCLen_US
dc.subjectDanvatirsenen_US
dc.subjectDurvalumaben_US
dc.subjectPhase 1en_US
dc.subjectSTAT3en_US
dc.titleA Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphomaen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.clml.2020.12.012
dc.identifier.pmid33632668
dc.source.countryUnited States


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