FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4286295057> ?p ?o ?g. }

• W4286295057 endingPage "4579" @default.
• W4286295057 startingPage "4579" @default.
• W4286295057 abstract "4579 Background: AXL is a member of the mammalian Tyro3/AXL/Mer (TAM) receptor tyrosine kinase family, which upon binding to its ligand Gas6 promotes immunosuppression in the tumor microenvironment. AVB-S6-500 (AVB) is a novel AXL pathway inhibitor which binds to circulating Gas6 and inhibits ligand-dependent AXL signaling. In this phase Ib investigator-initiated trial (NCT04004442), we evaluated the safety, tolerability, pharmacodynamics, and preliminary antitumor efficacy of AVB with the anti-PD-L1 antibody avelumab in mUC. Methods: Patients with PD-1/L1 inhibitor naïve locally advanced unresectable or mUC with measurable disease were eligible if they were either in-eligible for, refractory to, or declined platinum-based chemotherapy. Employing a 3+3 dose escalation design, patients were treated with AVB 5mg/kg weekly (dose level; DL1), or 10 (DL2), 15 (DL3), or 20 (DL4) mg/kg every two weeks along with avelumab 800 mg every 2 weeks administered intravenously. The safety and tolerability of the combination as measured by the incidence of dose limiting toxicities (DLTs) was the primary endpoint while objective response rate (ORR) per RECIST 1.1 was key secondary endpoint. Pharmacodynamic studies evaluated baseline and on therapy (C2D1) Gas6 levels. Results: To date, a total of 15 patients have been enrolled (DL1: n = 3, DL2: n = 7, DL3: n = 3 and DL4: n = 2). Among the 13 evaluable patients, DLT was observed in 1 patient (grade 3 fatigue; DL2). Grade ≥3 adverse events irrespective of attribution were seen in 6 patients which included UTI (n = 3), hyponatremia (n = 1), elevated creatinine (n = 1), and anemia, thrombocytopenia, hematuria, anorexia and sepsis (n = 1 each; all in same patient). No treatment related deaths were noted. While enrollment on DL4 is ongoing, the maximum tolerated dose for AVB has not been reached. Treatment with AVB effectively suppressed circulating Gas6 levels from baseline (median: 28.4 ng/mL; range: 20.4-54.0 ng/mL) to below threshold of detection in 85% (n = 11/13) of patients. Median follow up was 10 months (95% CI: 3.9, 18.55). Confirmed ORR was 38% (n = 5/13) while 1 patient had stable disease as best response. Durable responses lasting > 6 months were seen in 3 patients (7, 19 and 21 mos) who continue to be on treatment without disease progression. Additional correlative studies investigating AXL, Gas6, PD-L1 expression and gene expression signatures are currently underway. Conclusions: Concurrent avelumab and AVB was safe and AVB effectively neutralized circulating Gas6 across DLs. Albeit small sample size, the efficacy of the combination was encouraging and ORR compares favorably to that previously reported with PD-1/L1 inhibitor monotherapy. Updated safety, efficacy and biomarker data will be presented. Clinical trial information: NCT04004442." @default.
• W4286295057 created "2022-07-21" @default.
• W4286295057 creator A5003247790 @default.
• W4286295057 creator A5008599850 @default.
• W4286295057 creator A5041033274 @default.
• W4286295057 creator A5050663947 @default.
• W4286295057 creator A5052646705 @default.
• W4286295057 creator A5073077227 @default.
• W4286295057 creator A5079932513 @default.
• W4286295057 creator A5080507578 @default.
• W4286295057 creator A5084523168 @default.
• W4286295057 date "2022-06-01" @default.
• W4286295057 modified "2023-09-26" @default.
• W4286295057 title "Phase Ib study of avelumab and novel AXL inhibitor avb-S6-500 in patients with metastatic urothelial carcinoma (mUC)." @default.
• W4286295057 doi "https://doi.org/10.1200/jco.2022.40.16_suppl.4579" @default.
• W4286295057 hasPublicationYear "2022" @default.
• W4286295057 type Work @default.
• W4286295057 citedByCount "0" @default.
• W4286295057 crossrefType "journal-article" @default.
• W4286295057 hasAuthorship W4286295057A5003247790 @default.
• W4286295057 hasAuthorship W4286295057A5008599850 @default.
• W4286295057 hasAuthorship W4286295057A5041033274 @default.
• W4286295057 hasAuthorship W4286295057A5050663947 @default.
• W4286295057 hasAuthorship W4286295057A5052646705 @default.
• W4286295057 hasAuthorship W4286295057A5073077227 @default.
• W4286295057 hasAuthorship W4286295057A5079932513 @default.
• W4286295057 hasAuthorship W4286295057A5080507578 @default.
• W4286295057 hasAuthorship W4286295057A5084523168 @default.
• W4286295057 hasConcept C111113717 @default.
• W4286295057 hasConcept C112705442 @default.
• W4286295057 hasConcept C121608353 @default.
• W4286295057 hasConcept C126322002 @default.
• W4286295057 hasConcept C143998085 @default.
• W4286295057 hasConcept C197934379 @default.
• W4286295057 hasConcept C203092338 @default.
• W4286295057 hasConcept C2776694085 @default.
• W4286295057 hasConcept C2777381376 @default.
• W4286295057 hasConcept C2777701055 @default.
• W4286295057 hasConcept C2778375690 @default.
• W4286295057 hasConcept C2779984678 @default.
• W4286295057 hasConcept C2780057760 @default.
• W4286295057 hasConcept C31760486 @default.
• W4286295057 hasConcept C535046627 @default.
• W4286295057 hasConcept C71924100 @default.
• W4286295057 hasConcept C90924648 @default.
• W4286295057 hasConceptScore W4286295057C111113717 @default.
• W4286295057 hasConceptScore W4286295057C112705442 @default.
• W4286295057 hasConceptScore W4286295057C121608353 @default.
• W4286295057 hasConceptScore W4286295057C126322002 @default.
• W4286295057 hasConceptScore W4286295057C143998085 @default.
• W4286295057 hasConceptScore W4286295057C197934379 @default.
• W4286295057 hasConceptScore W4286295057C203092338 @default.
• W4286295057 hasConceptScore W4286295057C2776694085 @default.
• W4286295057 hasConceptScore W4286295057C2777381376 @default.
• W4286295057 hasConceptScore W4286295057C2777701055 @default.
• W4286295057 hasConceptScore W4286295057C2778375690 @default.
• W4286295057 hasConceptScore W4286295057C2779984678 @default.
• W4286295057 hasConceptScore W4286295057C2780057760 @default.
• W4286295057 hasConceptScore W4286295057C31760486 @default.
• W4286295057 hasConceptScore W4286295057C535046627 @default.
• W4286295057 hasConceptScore W4286295057C71924100 @default.
• W4286295057 hasConceptScore W4286295057C90924648 @default.
• W4286295057 hasIssue "16_suppl" @default.
• W4286295057 hasLocation W42862950571 @default.
• W4286295057 hasOpenAccess W4286295057 @default.
• W4286295057 hasPrimaryLocation W42862950571 @default.
• W4286295057 hasRelatedWork W1556562895 @default.
• W4286295057 hasRelatedWork W2194222775 @default.
• W4286295057 hasRelatedWork W2249326182 @default.
• W4286295057 hasRelatedWork W2806138002 @default.
• W4286295057 hasRelatedWork W3139770254 @default.
• W4286295057 hasRelatedWork W3193352205 @default.
• W4286295057 hasRelatedWork W3197516152 @default.
• W4286295057 hasRelatedWork W3210607323 @default.
• W4286295057 hasRelatedWork W3216317923 @default.
• W4286295057 hasRelatedWork W4366989399 @default.
• W4286295057 hasVolume "40" @default.
• W4286295057 isParatext "false" @default.
• W4286295057 isRetracted "false" @default.
• W4286295057 workType "article" @default.