FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4283784188> ?p ?o ?g. }

• W4283784188 endingPage "S294" @default.
• W4283784188 startingPage "S294" @default.
• W4283784188 abstract "A proprietary in vivo target discovery screen identified creatine kinase-B (CKB) as a cancer driver in KRAS mutant (KRAS-mut) CRC. CKB promotes tumor growth and survival under hypoxia. CKB generates the energetic metabolite phospho-creatine (PCr), which is imported into cells through the creatine transporter, SLC6A8. PCr generates intracellular ATP that enables tumoral survival. RGX-202-01 is a small molecule inhibitor of SLC6A8 that depletes intracellular PCr and ATP, resulting in apoptosis. In a completed phase 1a study, RGX-202-01 monotherapy demonstrated objective anti-tumor activity in the relapsed/refractory KRAS-mut CRC setting without dose-limiting toxicity. The objectives of this ongoing phase 1b study are to evaluate safety, PK/PD, and efficacy of RGX-202-01 in combination with standard-of-care (SOC) FOLFIRI + BEV in second-line CRC, a setting where SOC therapy results in an ORR and mPFS of approximately 15% and 6 months, respectively. Subjects with advanced CRC who had disease progression after receiving a first-line oxaliplatin-containing regimen were eligible. As of 02-24-2022, 17 patients (pts) have been enrolled. 8 pts were enrolled in 2 dose escalation cohorts of RGX-202-01: 2400mg BID (4 pts) and 3000mg BID (4 pts) combined with FOLFIRI and BEV. 9 pts were enrolled in the dose expansion phase of the study and received RGX-202-01 3000mg BID combined with FOLFIRI and BEV. No DLTs were observed and the MTD was not reached in the dose escalation phase. Most common G2 TRAEs were nausea and diarrhea (50%) and most common G3 TRAEs were fatigue (12%) and hypertension (12%) There were no Grade 4-5 TRAEs. At the RP2D of 3000 mg BID, PK analysis showed sustained RGX-202-01 drug exposures above target levels (IC50). In addition, Serum and urine creatine measurements indicated robust SLC6A8 target inhibition (in both escalation cohort). 9 pts had KRAS-mut CRC, and all were evaluable for RECIST 1.1 response. 5 of these pts had PR (confirmed) and 4 pts have SD as best response (ORR 56%, DCR 100%). 5 of these pts remain on study for a duration ranging from 15-58 weeks. One patient with a PR at 16 weeks had surgery with curative intent and was observed off therapy with no evidence of disease until week 44 when a CT identified a recurrence. 8 pts had KRAS WT CRC. Of the 5 KRAS WT pts evaluable for response, 1 has a PR on first scan and is ongoing and 4 pts have SD as best response. (ORR 20%, DCR 100%)3 patients remain on study at 8, 20 and 24 weeks respectively. RGX-202-01 combined with FOLFIRI and BEV was well tolerated with no DLTs at the dose levels evaluated which induced potent inhibition of SLC6A8. Encouraging efficacy was observed in patients with RAS mutate mCRC, with 56% response rate exceeding that expected with SOC. Preferential activity in patients with RAS mutated tumors is consistent with pre-clinical studies. Enrollment in the expansion phase continues and a phase 2/3 trial in 2L CRC with RAS mut is planned." @default.
• W4283784188 created "2022-07-04" @default.
• W4283784188 creator A5016155685 @default.
• W4283784188 creator A5018054038 @default.
• W4283784188 creator A5018755924 @default.
• W4283784188 creator A5027630636 @default.
• W4283784188 creator A5027943629 @default.
• W4283784188 creator A5031539570 @default.
• W4283784188 creator A5034045594 @default.
• W4283784188 creator A5035969070 @default.
• W4283784188 creator A5036647438 @default.
• W4283784188 creator A5054223542 @default.
• W4283784188 creator A5059364665 @default.
• W4283784188 creator A5061200817 @default.
• W4283784188 creator A5065416044 @default.
• W4283784188 creator A5066517223 @default.
• W4283784188 creator A5068156078 @default.
• W4283784188 creator A5068706033 @default.
• W4283784188 creator A5075778824 @default.
• W4283784188 creator A5077948323 @default.
• W4283784188 creator A5086781190 @default.
• W4283784188 creator A5090031886 @default.
• W4283784188 date "2022-06-01" @default.
• W4283784188 modified "2023-10-16" @default.
• W4283784188 title "P-125 Phase 1b study of RGX-202-01, a first-in-class oral inhibitor of the SLC6A8/CKB pathway, in combination with FOLFIRI and bevacizumab (BEV) in second-line advanced colorectal cancer (CRC)" @default.
• W4283784188 doi "https://doi.org/10.1016/j.annonc.2022.04.215" @default.
• W4283784188 hasPublicationYear "2022" @default.
• W4283784188 type Work @default.
• W4283784188 citedByCount "1" @default.
• W4283784188 countsByYear W42837841882023 @default.
• W4283784188 crossrefType "journal-article" @default.
• W4283784188 hasAuthorship W4283784188A5016155685 @default.
• W4283784188 hasAuthorship W4283784188A5018054038 @default.
• W4283784188 hasAuthorship W4283784188A5018755924 @default.
• W4283784188 hasAuthorship W4283784188A5027630636 @default.
• W4283784188 hasAuthorship W4283784188A5027943629 @default.
• W4283784188 hasAuthorship W4283784188A5031539570 @default.
• W4283784188 hasAuthorship W4283784188A5034045594 @default.
• W4283784188 hasAuthorship W4283784188A5035969070 @default.
• W4283784188 hasAuthorship W4283784188A5036647438 @default.
• W4283784188 hasAuthorship W4283784188A5054223542 @default.
• W4283784188 hasAuthorship W4283784188A5059364665 @default.
• W4283784188 hasAuthorship W4283784188A5061200817 @default.
• W4283784188 hasAuthorship W4283784188A5065416044 @default.
• W4283784188 hasAuthorship W4283784188A5066517223 @default.
• W4283784188 hasAuthorship W4283784188A5068156078 @default.
• W4283784188 hasAuthorship W4283784188A5068706033 @default.
• W4283784188 hasAuthorship W4283784188A5075778824 @default.
• W4283784188 hasAuthorship W4283784188A5077948323 @default.
• W4283784188 hasAuthorship W4283784188A5086781190 @default.
• W4283784188 hasAuthorship W4283784188A5090031886 @default.
• W4283784188 hasBestOaLocation W42837841881 @default.
• W4283784188 hasConcept C121608353 @default.
• W4283784188 hasConcept C126322002 @default.
• W4283784188 hasConcept C143998085 @default.
• W4283784188 hasConcept C2776694085 @default.
• W4283784188 hasConcept C2776705615 @default.
• W4283784188 hasConcept C2777802072 @default.
• W4283784188 hasConcept C2780259306 @default.
• W4283784188 hasConcept C2780962732 @default.
• W4283784188 hasConcept C2781187634 @default.
• W4283784188 hasConcept C2781413609 @default.
• W4283784188 hasConcept C29730261 @default.
• W4283784188 hasConcept C31760486 @default.
• W4283784188 hasConcept C526805850 @default.
• W4283784188 hasConcept C71924100 @default.
• W4283784188 hasConcept C90924648 @default.
• W4283784188 hasConcept C98274493 @default.
• W4283784188 hasConceptScore W4283784188C121608353 @default.
• W4283784188 hasConceptScore W4283784188C126322002 @default.
• W4283784188 hasConceptScore W4283784188C143998085 @default.
• W4283784188 hasConceptScore W4283784188C2776694085 @default.
• W4283784188 hasConceptScore W4283784188C2776705615 @default.
• W4283784188 hasConceptScore W4283784188C2777802072 @default.
• W4283784188 hasConceptScore W4283784188C2780259306 @default.
• W4283784188 hasConceptScore W4283784188C2780962732 @default.
• W4283784188 hasConceptScore W4283784188C2781187634 @default.
• W4283784188 hasConceptScore W4283784188C2781413609 @default.
• W4283784188 hasConceptScore W4283784188C29730261 @default.
• W4283784188 hasConceptScore W4283784188C31760486 @default.
• W4283784188 hasConceptScore W4283784188C526805850 @default.
• W4283784188 hasConceptScore W4283784188C71924100 @default.
• W4283784188 hasConceptScore W4283784188C90924648 @default.
• W4283784188 hasConceptScore W4283784188C98274493 @default.
• W4283784188 hasLocation W42837841881 @default.
• W4283784188 hasOpenAccess W4283784188 @default.
• W4283784188 hasPrimaryLocation W42837841881 @default.
• W4283784188 hasRelatedWork W2010928484 @default.
• W4283784188 hasRelatedWork W2014795358 @default.
• W4283784188 hasRelatedWork W2051540233 @default.
• W4283784188 hasRelatedWork W2071471252 @default.
• W4283784188 hasRelatedWork W2101986864 @default.
• W4283784188 hasRelatedWork W2591445974 @default.
• W4283784188 hasRelatedWork W2601872653 @default.
• W4283784188 hasRelatedWork W2617055067 @default.
• W4283784188 hasRelatedWork W2712978371 @default.
• W4283784188 hasRelatedWork W2939662662 @default.
• W4283784188 hasVolume "33" @default.

• next