FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4365513062> ?p ?o ?g. }

• W4365513062 endingPage "CT105" @default.
• W4365513062 startingPage "CT105" @default.
• W4365513062 abstract "Abstract Background: The dysregulation of polycomb repressive complex 2 (PRC2) promotes tumorigenesis and progression. Two therapeutic agents targeting enhancer of zeste homolog (EZH) 2 or EZH1/2, the catalytic subunits of PRC2, have been approved in several cancer types. HH2853 is a novel selective EZH1/2 dual inhibitor, which has demonstrated superior anti-tumor efficacy to tazemetostat (EZH2 inhibitor approved by FDA) in various preclinical models. Methods: This is a first-in-human, open-label, multi-center, phase (Ph) I/II study of HH2853 in patients (pts) with relapsed/refractory (r/r) non-Hodgkin lymphomas (NHLs) or advanced solid tumors. HH2853 was administered orally twice daily (BID) on a continuous 28-day treatment cycle. Ph I consist of two parts: dose escalation part adopting accelerated titration followed by a Bayesian optimal interval design and dose extension part. Dose limiting toxicity (DLT) was evaluated during the 1st cycle in dose escalation. Safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of HH2853 were explored in this Ph I study. Results: As of Oct 19, 2022, a total of 57 pts, including 50 pts with solid tumors and 7 pts with r/r follicular lymphoma (FL), were enrolled from 12 sites in China and the US. Twenty-five (43.9%) pts received ≥3 lines of prior systemic therapies. Six dose levels(50 mg, 100 mg, 200 mg, 400 mg, 600 mg and 800 mg)were evaluated. DLTs were observed in 2 of 8 DLT evaluable pts at 800 mg: one grade 3 platelet count decreased and one grade 3 diarrhea. A conclusive maximal tolerated dose was not reached. The most common treatment-related adverse events (TRAE) were diarrhea (45.6%), blood bilirubin increased (35.1%), white blood cell count (WBC) decreased (26.3%), platelet count decreased (26.3%), rash (24.6%) and anemia (22.8%). The most common ≥grade 3 TRAEs included anemia (8.8%), platelet count decreased (7.0%), WBC decreased (5.3%) and diarrhea (5.3%). TRAEs leading to dose interruption or reduction were reported in 17.5% and 8.8% pts respectively. No TRAE led to dose discontinuation or death. PK data indicated dose-related increase in exposure from 50 to 600 mg. PD data showed a significant inhibition (maximum reached &gt;90%) of H3K27me3 in granulocytes and monocytes at 400-800 mg. Tumor responses were observed in 7 pts from 200 to 800 mg in multiple tumor types, including complete response in 1 patient with FL, partial response in 3 pts with epithelioid sarcoma, 2 pts with FL and 1 patient with malignant rhabdoid tumor of pancreas. Conclusions: This first-in-human study of HH2853 showed a manageable safety profile and promising anti-tumor activity in multiple tumor types, supporting further exploration in NHLs and solid tumors after recommended Ph II dose is determined.Clinical trial information: NCT04390737 Citation Format: Zhengfu Fan, Jin Wang, Meiyu Fang, Johnston Patrick, Tun Han, David Sommerhalder, Jifang Gong, Jilong Yang, Yun Yang, Javier Munoz, Yuqin Song, Zhiming Li, Xian'an Li, Qiuying Ma, Jinming Han, Lin Shen, Jun Zhu. Preliminary results from the Phase I part of a first-in-human Phase I/II study of HH2853, an EZH1/2 inhibitor, in patients with relapsed/refractory non-Hodgkin lymphomas or advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT105." @default.
• W4365513062 created "2023-04-15" @default.
• W4365513062 creator A5001561478 @default.
• W4365513062 creator A5004358361 @default.
• W4365513062 creator A5006511913 @default.
• W4365513062 creator A5018244700 @default.
• W4365513062 creator A5019659276 @default.
• W4365513062 creator A5019942645 @default.
• W4365513062 creator A5029795696 @default.
• W4365513062 creator A5030200922 @default.
• W4365513062 creator A5030829302 @default.
• W4365513062 creator A5049646905 @default.
• W4365513062 creator A5059757962 @default.
• W4365513062 creator A5061006889 @default.
• W4365513062 creator A5063897579 @default.
• W4365513062 creator A5064823422 @default.
• W4365513062 creator A5076892547 @default.
• W4365513062 creator A5086637275 @default.
• W4365513062 creator A5090442154 @default.
• W4365513062 date "2023-04-14" @default.
• W4365513062 modified "2023-10-16" @default.
• W4365513062 title "Abstract CT105: Preliminary results from the Phase I part of a first-in-human Phase I/II study of HH2853, an EZH1/2 inhibitor, in patients with relapsed/refractory non-Hodgkin lymphomas or advanced solid tumors" @default.
• W4365513062 doi "https://doi.org/10.1158/1538-7445.am2023-ct105" @default.
• W4365513062 hasPublicationYear "2023" @default.
• W4365513062 type Work @default.
• W4365513062 citedByCount "0" @default.
• W4365513062 crossrefType "journal-article" @default.
• W4365513062 hasAuthorship W4365513062A5001561478 @default.
• W4365513062 hasAuthorship W4365513062A5004358361 @default.
• W4365513062 hasAuthorship W4365513062A5006511913 @default.
• W4365513062 hasAuthorship W4365513062A5018244700 @default.
• W4365513062 hasAuthorship W4365513062A5019659276 @default.
• W4365513062 hasAuthorship W4365513062A5019942645 @default.
• W4365513062 hasAuthorship W4365513062A5029795696 @default.
• W4365513062 hasAuthorship W4365513062A5030200922 @default.
• W4365513062 hasAuthorship W4365513062A5030829302 @default.
• W4365513062 hasAuthorship W4365513062A5049646905 @default.
• W4365513062 hasAuthorship W4365513062A5059757962 @default.
• W4365513062 hasAuthorship W4365513062A5061006889 @default.
• W4365513062 hasAuthorship W4365513062A5063897579 @default.
• W4365513062 hasAuthorship W4365513062A5064823422 @default.
• W4365513062 hasAuthorship W4365513062A5076892547 @default.
• W4365513062 hasAuthorship W4365513062A5086637275 @default.
• W4365513062 hasAuthorship W4365513062A5090442154 @default.
• W4365513062 hasConcept C111113717 @default.
• W4365513062 hasConcept C112705442 @default.
• W4365513062 hasConcept C121332964 @default.
• W4365513062 hasConcept C126322002 @default.
• W4365513062 hasConcept C142424586 @default.
• W4365513062 hasConcept C143998085 @default.
• W4365513062 hasConcept C197934379 @default.
• W4365513062 hasConcept C22979827 @default.
• W4365513062 hasConcept C2777058707 @default.
• W4365513062 hasConcept C2778375690 @default.
• W4365513062 hasConcept C2779338263 @default.
• W4365513062 hasConcept C2779984678 @default.
• W4365513062 hasConcept C29730261 @default.
• W4365513062 hasConcept C31760486 @default.
• W4365513062 hasConcept C71924100 @default.
• W4365513062 hasConcept C87355193 @default.
• W4365513062 hasConcept C90924648 @default.
• W4365513062 hasConcept C98274493 @default.
• W4365513062 hasConceptScore W4365513062C111113717 @default.
• W4365513062 hasConceptScore W4365513062C112705442 @default.
• W4365513062 hasConceptScore W4365513062C121332964 @default.
• W4365513062 hasConceptScore W4365513062C126322002 @default.
• W4365513062 hasConceptScore W4365513062C142424586 @default.
• W4365513062 hasConceptScore W4365513062C143998085 @default.
• W4365513062 hasConceptScore W4365513062C197934379 @default.
• W4365513062 hasConceptScore W4365513062C22979827 @default.
• W4365513062 hasConceptScore W4365513062C2777058707 @default.
• W4365513062 hasConceptScore W4365513062C2778375690 @default.
• W4365513062 hasConceptScore W4365513062C2779338263 @default.
• W4365513062 hasConceptScore W4365513062C2779984678 @default.
• W4365513062 hasConceptScore W4365513062C29730261 @default.
• W4365513062 hasConceptScore W4365513062C31760486 @default.
• W4365513062 hasConceptScore W4365513062C71924100 @default.
• W4365513062 hasConceptScore W4365513062C87355193 @default.
• W4365513062 hasConceptScore W4365513062C90924648 @default.
• W4365513062 hasConceptScore W4365513062C98274493 @default.
• W4365513062 hasIssue "8_Supplement" @default.
• W4365513062 hasLocation W43655130621 @default.
• W4365513062 hasOpenAccess W4365513062 @default.
• W4365513062 hasPrimaryLocation W43655130621 @default.
• W4365513062 hasRelatedWork W1822154343 @default.
• W4365513062 hasRelatedWork W2014468166 @default.
• W4365513062 hasRelatedWork W2074207917 @default.
• W4365513062 hasRelatedWork W2112620969 @default.
• W4365513062 hasRelatedWork W2626992247 @default.
• W4365513062 hasRelatedWork W2914758292 @default.
• W4365513062 hasRelatedWork W2922882148 @default.
• W4365513062 hasRelatedWork W3135415338 @default.
• W4365513062 hasRelatedWork W4319063555 @default.
• W4365513062 hasRelatedWork W4321478834 @default.
• W4365513062 hasVolume "83" @default.
• W4365513062 isParatext "false" @default.
• W4365513062 isRetracted "false" @default.
• W4365513062 workType "article" @default.