FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308383771> ?p ?o ?g. }

• W4308383771 abstract "<h3>Background</h3> PD-1/PD-L1 inhibitors (PD-(L)1i) have improved outcomes for many patients with advanced malignancies; however, most do not respond, or fail to achieve durable anti-tumor immunity. PD-1-mediated inhibition of T-cell effector function works primarily by inactivating the CD28 costimulatory signal. While PD-(L)1i can remove such inhibition, active CD28 costimulation is likely still required for optimal T-cell activation. Davoceticept is a variant CD80 vIgD-Fc fusion protein, engineered to provide PD-L1-dependent CD28 costimulation, while inhibiting PD-1 and CTLA-4. In NEON-1 (NCT04186637), davoceticept monotherapy was well-tolerated up to 10mg/kg, Q3W, and showed evidence of clinical activity in papillary renal cell carcinoma (RCC). A davoceticept + PD-1i approach is supported by preclinical models where combination treatment yielded tumor volume reductions beyond those seen with either monotherapy. Further, PD-1 inhibition may up-regulate PD-L1 in the tumor and sensitize it to PD–L1-dependent CD28 costimulation by davoceticept. <h3>Methods</h3> NEON-2 is an open-label dose escalation and expansion study of davoceticept + pembrolizumab in adults with advanced solid tumors or lymphoma (NCT04920383). Eligibility includes tumors for which single agent PD-(L)1i are standard of care, are refractory/resistant to standard therapies, or have no standard or curative treatments available. The study employs a standard 3+3 dose-escalation design with 2 schedules of intravenous (IV) davoceticept: Q1W and Q3W. Pembrolizumab is given per label at 400mg IV Q6W. Study objectives include evaluation of safety and tolerability, identification of the recommended phase 2 dose(s) (RP2D), pharmacokinetic, pharmacodynamic, exploratory biomarker analyses, and preliminary efficacy. <h3>Results</h3> As of June 2022, 19 subjects have been treated with davoceticept in dose escalation at 0.1 and 0.3mg/kg, Q1W and Q3W. Seven subjects experienced a total of 9 Grade 3+ treatment–related adverse events, including one Grade 5 cardiogenic shock in the 0.3mg/kg, Q3W cohort. Gr3+ immune-related adverse events were more common in subjects receiving 0.3 vs. 0.1mg/kg regimens of davoceticept, at 27.3% and 12.5%, respectively. Of 14 evaluable subjects, 1 confirmed partial response has been observed in a nivolumab-experienced subject with clear cell RCC. Additionally, tumor reductions have been noted in a second ongoing RCC subject, and in subjects with prostate cancer and serous peritoneal carcinoma. Fifty percent of evaluable subjects achieved a best response of stable disease. <h3>Conclusions</h3> The davoceticept + pembrolizumab combination has demonstrated preliminary anti-tumor activity in clear cell RCC, potentially by reversing resistance to PD-(L)1i. Dose escalation efforts will resume at 0.1mg/kg, Q1W and Q3W. Tumor-specific expansion cohorts will open once the RP2D/schedule of the combination treatment is identified. <h3>Trial Registration</h3> NCT04920383 <h3>Ethics Approval</h3> This study received ethics approval from the WCG IRB (Sarah Cannon; ID 20211877), Salus IRB (START Texas; ID START2021.28, START Midwest; ID STMW2021.18), and Mass General Brigham IRB (Massachusetts General Hospital; ID 2021P002079). All study subjects provided their informed consent to participate in this study." @default.
• W4308383771 created "2022-11-11" @default.
• W4308383771 creator A5002575629 @default.
• W4308383771 creator A5003770647 @default.
• W4308383771 creator A5014629304 @default.
• W4308383771 creator A5022348809 @default.
• W4308383771 creator A5025149042 @default.
• W4308383771 creator A5035788052 @default.
• W4308383771 creator A5038887077 @default.
• W4308383771 creator A5047883586 @default.
• W4308383771 creator A5061391765 @default.
• W4308383771 creator A5064537078 @default.
• W4308383771 creator A5070570779 @default.
• W4308383771 creator A5078432808 @default.
• W4308383771 creator A5081227348 @default.
• W4308383771 date "2022-11-01" @default.
• W4308383771 modified "2023-09-26" @default.
• W4308383771 title "738 Interim dose escalation of davoceticept, a conditional CD28 costimulator and dual checkpoint inhibitor, in combination with pembrolizumab in advanced malignancies (NEON-2)" @default.
• W4308383771 doi "https://doi.org/10.1136/jitc-2022-sitc2022.0738" @default.
• W4308383771 hasPublicationYear "2022" @default.
• W4308383771 type Work @default.
• W4308383771 citedByCount "0" @default.
• W4308383771 crossrefType "proceedings-article" @default.
• W4308383771 hasAuthorship W4308383771A5002575629 @default.
• W4308383771 hasAuthorship W4308383771A5003770647 @default.
• W4308383771 hasAuthorship W4308383771A5014629304 @default.
• W4308383771 hasAuthorship W4308383771A5022348809 @default.
• W4308383771 hasAuthorship W4308383771A5025149042 @default.
• W4308383771 hasAuthorship W4308383771A5035788052 @default.
• W4308383771 hasAuthorship W4308383771A5038887077 @default.
• W4308383771 hasAuthorship W4308383771A5047883586 @default.
• W4308383771 hasAuthorship W4308383771A5061391765 @default.
• W4308383771 hasAuthorship W4308383771A5064537078 @default.
• W4308383771 hasAuthorship W4308383771A5070570779 @default.
• W4308383771 hasAuthorship W4308383771A5078432808 @default.
• W4308383771 hasAuthorship W4308383771A5081227348 @default.
• W4308383771 hasBestOaLocation W43083837711 @default.
• W4308383771 hasConcept C121608353 @default.
• W4308383771 hasConcept C126322002 @default.
• W4308383771 hasConcept C143998085 @default.
• W4308383771 hasConcept C148125776 @default.
• W4308383771 hasConcept C154317977 @default.
• W4308383771 hasConcept C185592680 @default.
• W4308383771 hasConcept C202751555 @default.
• W4308383771 hasConcept C203014093 @default.
• W4308383771 hasConcept C2776090121 @default.
• W4308383771 hasConcept C2777701055 @default.
• W4308383771 hasConcept C2778297628 @default.
• W4308383771 hasConcept C2780057760 @default.
• W4308383771 hasConcept C2781053074 @default.
• W4308383771 hasConcept C39347974 @default.
• W4308383771 hasConcept C502942594 @default.
• W4308383771 hasConcept C55493867 @default.
• W4308383771 hasConcept C71924100 @default.
• W4308383771 hasConcept C8891405 @default.
• W4308383771 hasConceptScore W4308383771C121608353 @default.
• W4308383771 hasConceptScore W4308383771C126322002 @default.
• W4308383771 hasConceptScore W4308383771C143998085 @default.
• W4308383771 hasConceptScore W4308383771C148125776 @default.
• W4308383771 hasConceptScore W4308383771C154317977 @default.
• W4308383771 hasConceptScore W4308383771C185592680 @default.
• W4308383771 hasConceptScore W4308383771C202751555 @default.
• W4308383771 hasConceptScore W4308383771C203014093 @default.
• W4308383771 hasConceptScore W4308383771C2776090121 @default.
• W4308383771 hasConceptScore W4308383771C2777701055 @default.
• W4308383771 hasConceptScore W4308383771C2778297628 @default.
• W4308383771 hasConceptScore W4308383771C2780057760 @default.
• W4308383771 hasConceptScore W4308383771C2781053074 @default.
• W4308383771 hasConceptScore W4308383771C39347974 @default.
• W4308383771 hasConceptScore W4308383771C502942594 @default.
• W4308383771 hasConceptScore W4308383771C55493867 @default.
• W4308383771 hasConceptScore W4308383771C71924100 @default.
• W4308383771 hasConceptScore W4308383771C8891405 @default.
• W4308383771 hasLocation W43083837711 @default.
• W4308383771 hasOpenAccess W4308383771 @default.
• W4308383771 hasPrimaryLocation W43083837711 @default.
• W4308383771 hasRelatedWork W2155756052 @default.
• W4308383771 hasRelatedWork W2786497694 @default.
• W4308383771 hasRelatedWork W2804110341 @default.
• W4308383771 hasRelatedWork W2899426010 @default.
• W4308383771 hasRelatedWork W2969782175 @default.
• W4308383771 hasRelatedWork W3043416314 @default.
• W4308383771 hasRelatedWork W3215044659 @default.
• W4308383771 hasRelatedWork W4308383771 @default.
• W4308383771 hasRelatedWork W4361938501 @default.
• W4308383771 hasRelatedWork W4362546138 @default.
• W4308383771 isParatext "false" @default.
• W4308383771 isRetracted "false" @default.
• W4308383771 workType "article" @default.