FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4382806768> ?p ?o ?g. }

• W4382806768 endingPage "S161" @default.
• W4382806768 startingPage "S161" @default.
• W4382806768 abstract "IDH1 and 2 (IDH1/2) are mutated in 10-15% of intrahepatic cholangiocarcinoma (CCA). The reversible IDH1 inhibitor ivosidenib is approved in 2L IDH1-mutant CCA. Cisplatin and gemcitabine (CISGEM) is the standard 1L chemotherapy backbone for advanced CCA. Addition of PD1/PDL1 inhibitors have demonstrated modest improvement in OS (median 12.8 months), highlighting ongoing unmet need. LY3410738 is an oral, potent, selective, dual inhibitor of IDH1/2 mutations (IDH1/2m). LY3410738 binds covalently at a novel binding site, enabling continued potency in preclinical models in the setting of second site IDH resistance mutations. Here, we present the translational in vivo findings and data from the ongoing phase 1 study of LY3410738 as monotherapy and with CISGEM in advanced IDH1/2m CCA (NCT04521686). In the phase 1 study, dose escalation (3+3 design) evaluated LY3410738 monotherapy in advanced relapsed/refractory (R/R) IDH1/2m CCA and other solid tumors. Dose expansion evaluated LY3410738 in combination with CISGEM in treatment naïve advanced IDH1/2m CCA patients. Objectives included determining the RP2D, safety, PK/PD, and antitumor activity. In an IDH1m CCA PDX model, single agent LY3410738 (10-30 mpk, QD) demonstrated >60% tumor growth inhibition. In a combination PDX study, LY3410738 (30 mpk, QD) plus CISGEM (3/60 mpk, Q7Dx3, 3/40mpk, Q7Dx3) treatment for 6 weeks followed by 15 weeks of LY3410738 maintenance led to 85% tumor growth inhibition, while CISGEM alone achieved only 47% tumor growth inhibition (p < 0.001). In the phase 1 dose escalation cohorts, as of November 01, 2022, 45 patients with R/R CCA received LY3410738 monotherapy (25 - 600 mg QD or 150 - 300 mg BID) (1). Median number of prior lines of therapy was 2 (range, 1-7). The ORR was 4.5% with 2 PR and 23 SD. mPFS was 3.5 months (95% CI, 1.9-5.1). 6 months PFS rate was 32.5% (95% CI 18.8-47.0). In the dose expansion cohort, 13 patients with treatment naïve advanced CCA received LY3410738 (300 mg BID or 400 mg QD) in combination with CISGEM. The median age was 64 years (range, 51-77). Median time on treatment was 5.95 months (range, 2.3-9.1). No DLTs were observed. TEAE ≥30% regardless of attribution were anemia (54%), platelet count decreased (54%), nausea (46%), decreased appetite (39%), neutrophil count decreased (39%), and constipation (31%). Most frequent grade ≥3 TEAE ≥25% were neutrophil count decreased (39%), platelet count decreased (39%), and anemia (31%). 7 (54%) patients reported LY3410738 related AEs of which nausea and neutrophil count decreased were grade 3. The ORR was 46% with 6 PR/uPR (pending confirmation and ongoing) and 6 SD. mPFS was not reached, and 6 months PFS rate was 83.3% (95% CI, 27.3-97.5). The PK/PD profiles were consistent with LY3410738 monotherapy (1). In this phase 1 study, LY3410738 in combination with CISGEM demonstrated a favorable safety profile and preliminary efficacy in treatment naïve locally advanced or metastatic IDH1/2m CCA. RP2D evaluation is ongoing. Reference: 1. Rodon J. et al. To be presented at AACR 2023, Apr 14-19." @default.
• W4382806768 created "2023-07-02" @default.
• W4382806768 creator A5000636193 @default.
• W4382806768 creator A5004548381 @default.
• W4382806768 creator A5012936802 @default.
• W4382806768 creator A5022537134 @default.
• W4382806768 creator A5024331685 @default.
• W4382806768 creator A5034270737 @default.
• W4382806768 creator A5037548278 @default.
• W4382806768 creator A5043503183 @default.
• W4382806768 creator A5045084904 @default.
• W4382806768 creator A5050530209 @default.
• W4382806768 creator A5052192859 @default.
• W4382806768 creator A5052788724 @default.
• W4382806768 creator A5058524907 @default.
• W4382806768 creator A5058709133 @default.
• W4382806768 creator A5059766169 @default.
• W4382806768 creator A5065435809 @default.
• W4382806768 creator A5074025663 @default.
• W4382806768 creator A5077771845 @default.
• W4382806768 creator A5078041270 @default.
• W4382806768 creator A5082191671 @default.
• W4382806768 creator A5086593040 @default.
• W4382806768 date "2023-06-01" @default.
• W4382806768 modified "2023-10-15" @default.
• W4382806768 title "SO-1 A first-in-human phase 1 study of LY3410738, a covalent inhibitor of mutant IDH1 and IDH2, as monotherapy and in combination with cisplatin and gemcitabine in advanced IDH-mutant cholangiocarcinoma" @default.
• W4382806768 doi "https://doi.org/10.1016/j.annonc.2023.04.473" @default.
• W4382806768 hasPublicationYear "2023" @default.
• W4382806768 type Work @default.
• W4382806768 citedByCount "0" @default.
• W4382806768 crossrefType "journal-article" @default.
• W4382806768 hasAuthorship W4382806768A5000636193 @default.
• W4382806768 hasAuthorship W4382806768A5004548381 @default.
• W4382806768 hasAuthorship W4382806768A5012936802 @default.
• W4382806768 hasAuthorship W4382806768A5022537134 @default.
• W4382806768 hasAuthorship W4382806768A5024331685 @default.
• W4382806768 hasAuthorship W4382806768A5034270737 @default.
• W4382806768 hasAuthorship W4382806768A5037548278 @default.
• W4382806768 hasAuthorship W4382806768A5043503183 @default.
• W4382806768 hasAuthorship W4382806768A5045084904 @default.
• W4382806768 hasAuthorship W4382806768A5050530209 @default.
• W4382806768 hasAuthorship W4382806768A5052192859 @default.
• W4382806768 hasAuthorship W4382806768A5052788724 @default.
• W4382806768 hasAuthorship W4382806768A5058524907 @default.
• W4382806768 hasAuthorship W4382806768A5058709133 @default.
• W4382806768 hasAuthorship W4382806768A5059766169 @default.
• W4382806768 hasAuthorship W4382806768A5065435809 @default.
• W4382806768 hasAuthorship W4382806768A5074025663 @default.
• W4382806768 hasAuthorship W4382806768A5077771845 @default.
• W4382806768 hasAuthorship W4382806768A5078041270 @default.
• W4382806768 hasAuthorship W4382806768A5082191671 @default.
• W4382806768 hasAuthorship W4382806768A5086593040 @default.
• W4382806768 hasBestOaLocation W43828067681 @default.
• W4382806768 hasConcept C104317684 @default.
• W4382806768 hasConcept C126322002 @default.
• W4382806768 hasConcept C127848430 @default.
• W4382806768 hasConcept C143065580 @default.
• W4382806768 hasConcept C143998085 @default.
• W4382806768 hasConcept C150903083 @default.
• W4382806768 hasConcept C185592680 @default.
• W4382806768 hasConcept C207001950 @default.
• W4382806768 hasConcept C2776059313 @default.
• W4382806768 hasConcept C2776694085 @default.
• W4382806768 hasConcept C2776999253 @default.
• W4382806768 hasConcept C2778239845 @default.
• W4382806768 hasConcept C2780258809 @default.
• W4382806768 hasConcept C31760486 @default.
• W4382806768 hasConcept C502942594 @default.
• W4382806768 hasConcept C55493867 @default.
• W4382806768 hasConcept C71924100 @default.
• W4382806768 hasConcept C86803240 @default.
• W4382806768 hasConcept C98274493 @default.
• W4382806768 hasConceptScore W4382806768C104317684 @default.
• W4382806768 hasConceptScore W4382806768C126322002 @default.
• W4382806768 hasConceptScore W4382806768C127848430 @default.
• W4382806768 hasConceptScore W4382806768C143065580 @default.
• W4382806768 hasConceptScore W4382806768C143998085 @default.
• W4382806768 hasConceptScore W4382806768C150903083 @default.
• W4382806768 hasConceptScore W4382806768C185592680 @default.
• W4382806768 hasConceptScore W4382806768C207001950 @default.
• W4382806768 hasConceptScore W4382806768C2776059313 @default.
• W4382806768 hasConceptScore W4382806768C2776694085 @default.
• W4382806768 hasConceptScore W4382806768C2776999253 @default.
• W4382806768 hasConceptScore W4382806768C2778239845 @default.
• W4382806768 hasConceptScore W4382806768C2780258809 @default.
• W4382806768 hasConceptScore W4382806768C31760486 @default.
• W4382806768 hasConceptScore W4382806768C502942594 @default.
• W4382806768 hasConceptScore W4382806768C55493867 @default.
• W4382806768 hasConceptScore W4382806768C71924100 @default.
• W4382806768 hasConceptScore W4382806768C86803240 @default.
• W4382806768 hasConceptScore W4382806768C98274493 @default.
• W4382806768 hasLocation W43828067681 @default.
• W4382806768 hasOpenAccess W4382806768 @default.
• W4382806768 hasPrimaryLocation W43828067681 @default.
• W4382806768 hasRelatedWork W2026791198 @default.
• W4382806768 hasRelatedWork W2085978374 @default.
• W4382806768 hasRelatedWork W2100029565 @default.
• W4382806768 hasRelatedWork W2349270370 @default.

• next