FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4310117676> ?p ?o ?g. }

• W4310117676 endingPage "3747" @default.
• W4310117676 startingPage "3746" @default.
• W4310117676 abstract "Background Systemic glucocorticosteroids (ie, glucocorticoid receptor modulators [GRMs]) show robust monotherapy activity against B-cell malignancies at high doses; however, they may be accompanied by steroid-associated toxicities that limit dosing. CD19 is a marker essential for B-cell proliferation and has high expression across B-cell malignancies including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). ABBV-319 is a CD19-GRM antibody-drug conjugate (ADC) composed of an optimized high-affinity immunoglobulin G1 antibody conjugated to a potent proprietary glucocorticosteroid payload. ABBV-319 takes advantage of both enhanced antibody-dependent cellular cytotoxicity (via afucosylation) and targeted GRM payload delivery to maximize anticancer activity while lowering the risk of systemic steroid toxicities. Preclinically, ABBV-319 demonstrates sustained antitumor efficacy in models of human B-cell malignancies that compares favorably with approved therapeutics. This phase 1 study evaluates safety and clinical activity of ABBV-319 monotherapy in patients with relapsed or refractory (R/R) B-cell malignancies. Methods This is a phase 1, first-in-human, open-label, dose-escalation, dose-expansion, biomarker/pharmacodynamic (PD) study in patients aged ≥18 years with R/R B-cell malignancies. Key eligibility criteria include measurable disease and Eastern Cooperative Oncology Group performance status of 0 or 1. In addition, patients must meet predefined criteria for adrenal, bone marrow, kidney, and liver function, coagulation parameter levels, and hemoglobin A1c levels (dose escalation only) during screening. The primary objectives are to evaluate safety, tolerability, pharmacokinetics (PK), and immunogenicity of ABBV-319 and identify a recommended phase 2 dose (RP2D). The secondary objective is to evaluate the efficacy of ABBV-319 in patients with R/R DLBCL, FL, and CLL. Exploratory objectives include evaluating the effect of ABBV-319 on QT prolongation and evaluating PD and predictive biomarkers. This study will be conducted in 2 parts - dose escalation (Part 1) and dose expansion (Part 2). Part 1 aims to determine the RP2D for ABBV-319 following a Bayesian optimal interval design, with a maximum of 2-fold increments that reduce as the dose increases. RP2D will be determined on the basis of all the data collected in Part 1 including safety, tolerability, PK, PD, and efficacy, if available. Part 2 will further evaluate ABBV-319 at the RP2D in 3 separate subtypes of B-cell malignancies - DLBCL, FL, and CLL. A total of 114 patients are planned to be enrolled - 54 patients with various R/R B-cell malignancies in Part 1, and 60 patients in Part 2 (20 patients included for each R/R B-cell malignancy subtype: DLBCL, FL, and CLL). ABBV-319 will be administered intravenously until disease progression, intolerable toxicity, or other study discontinuation criteria are met, for a maximum of ~24 months from the last patient enrolled. Safety assessments include adverse event monitoring (per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0), physical examinations, vital sign measurements, and clinical laboratory testing. Dose-limiting toxicities will be assessed. PK parameters including maximum observed serum/plasma concentration (Cmax), time to Cmax, terminal plasma elimination half-life, and area under the serum/plasma concentration-time curve will be analyzed using noncompartmental methods for ABBV-319 total antibody, ADC, and unconjugated GRM payload. Antidrug antibodies (ADAs) and neutralizing ADAs may also be determined, as appropriate. Efficacy will be evaluated in terms of response per disease-specific criteria (including International Workshop on Chronic Lymphocytic Leukemia, International Workshop on Waldenstrom's Macroglobulinemia, and Lugano classification). Duration of response, time to response, progression-free survival, and overall survival will be evaluated per Kaplan-Meier analysis. QT prolongation, PD, and biomarker data will be assessed as changes from baseline and may be summarized for each scheduled postbaseline visit." @default.
• W4310117676 created "2022-11-30" @default.
• W4310117676 creator A5008433542 @default.
• W4310117676 creator A5010539676 @default.
• W4310117676 creator A5040849275 @default.
• W4310117676 creator A5044063447 @default.
• W4310117676 creator A5051783383 @default.
• W4310117676 creator A5058733601 @default.
• W4310117676 creator A5064969901 @default.
• W4310117676 creator A5078527108 @default.
• W4310117676 creator A5083858828 @default.
• W4310117676 date "2022-11-15" @default.
• W4310117676 modified "2023-09-28" @default.
• W4310117676 title "A First-in-Human Phase 1 Study of Abbv-319, an Antibody-Drug Conjugate Composed of a CD19 Antibody Linked to a Potent Proprietary Glucocorticoid Receptor Modulator, in Patients with Relapsed or Refractory B-Cell Malignancies" @default.
• W4310117676 doi "https://doi.org/10.1182/blood-2022-166809" @default.
• W4310117676 hasPublicationYear "2022" @default.
• W4310117676 type Work @default.
• W4310117676 citedByCount "0" @default.
• W4310117676 crossrefType "journal-article" @default.
• W4310117676 hasAuthorship W4310117676A5008433542 @default.
• W4310117676 hasAuthorship W4310117676A5010539676 @default.
• W4310117676 hasAuthorship W4310117676A5040849275 @default.
• W4310117676 hasAuthorship W4310117676A5044063447 @default.
• W4310117676 hasAuthorship W4310117676A5051783383 @default.
• W4310117676 hasAuthorship W4310117676A5058733601 @default.
• W4310117676 hasAuthorship W4310117676A5064969901 @default.
• W4310117676 hasAuthorship W4310117676A5078527108 @default.
• W4310117676 hasAuthorship W4310117676A5083858828 @default.
• W4310117676 hasConcept C126322002 @default.
• W4310117676 hasConcept C143998085 @default.
• W4310117676 hasConcept C159654299 @default.
• W4310117676 hasConcept C203014093 @default.
• W4310117676 hasConcept C2777058707 @default.
• W4310117676 hasConcept C2777325958 @default.
• W4310117676 hasConcept C2777938653 @default.
• W4310117676 hasConcept C2778453870 @default.
• W4310117676 hasConcept C2778461978 @default.
• W4310117676 hasConcept C2779338263 @default.
• W4310117676 hasConcept C502942594 @default.
• W4310117676 hasConcept C542903549 @default.
• W4310117676 hasConcept C71924100 @default.
• W4310117676 hasConcept C98274493 @default.
• W4310117676 hasConceptScore W4310117676C126322002 @default.
• W4310117676 hasConceptScore W4310117676C143998085 @default.
• W4310117676 hasConceptScore W4310117676C159654299 @default.
• W4310117676 hasConceptScore W4310117676C203014093 @default.
• W4310117676 hasConceptScore W4310117676C2777058707 @default.
• W4310117676 hasConceptScore W4310117676C2777325958 @default.
• W4310117676 hasConceptScore W4310117676C2777938653 @default.
• W4310117676 hasConceptScore W4310117676C2778453870 @default.
• W4310117676 hasConceptScore W4310117676C2778461978 @default.
• W4310117676 hasConceptScore W4310117676C2779338263 @default.
• W4310117676 hasConceptScore W4310117676C502942594 @default.
• W4310117676 hasConceptScore W4310117676C542903549 @default.
• W4310117676 hasConceptScore W4310117676C71924100 @default.
• W4310117676 hasConceptScore W4310117676C98274493 @default.
• W4310117676 hasIssue "Supplement 1" @default.
• W4310117676 hasLocation W43101176761 @default.
• W4310117676 hasOpenAccess W4310117676 @default.
• W4310117676 hasPrimaryLocation W43101176761 @default.
• W4310117676 hasRelatedWork W2007279260 @default.
• W4310117676 hasRelatedWork W2035676378 @default.
• W4310117676 hasRelatedWork W2091876239 @default.
• W4310117676 hasRelatedWork W2103359643 @default.
• W4310117676 hasRelatedWork W2140137149 @default.
• W4310117676 hasRelatedWork W2169593728 @default.
• W4310117676 hasRelatedWork W2239500937 @default.
• W4310117676 hasRelatedWork W2588652961 @default.
• W4310117676 hasRelatedWork W2805093224 @default.
• W4310117676 hasRelatedWork W29500930 @default.
• W4310117676 hasVolume "140" @default.
• W4310117676 isParatext "false" @default.
• W4310117676 isRetracted "false" @default.
• W4310117676 workType "article" @default.