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• W4295819095 abstract "M6223 is a human, intravenously (IV) administered, antagonistic, anti-TIGIT antibody. This is a first-in-human dose escalation (DE) study of M6223 (NCT04457778) as monotherapy or combined with BA in pts ≥18 years with ECOG PS ≤1 and advanced solid tumours, for whom no known effective therapy is available. In monotherapy DE, pts received M6223 at 1 of 7 dose levels (DLs): 10‒1600 mg every two weeks (Q2W) or 2400 mg every three weeks (Q3W). In combination, pts received M6223 at 1 of 3 DLs (300, 900, 1600 mg Q2W) with BA 1200 mg IV Q2W. Doses were recommended by the SMC, supported by a Bayesian 2-parameter logistic regression model. The trial is ongoing and additional pts will be enrolled to receive monotherapy to collect biomarker data from paired biopsies (DL 2400 mg Q3W; DLs 900 and 1600 mg Q2W). Primary objectives are safety, tolerability, maximum tolerated dose, and recommended dose for expansion (RDE) of M6223 mono- and combination therapy (M6223 + BA). Secondary and exploratory objectives include pharmacokinetics (PK), clinical activity and biomarkers. We report preliminary interim data. By April 1, 2022, 24 pts (10 male, 14 female; age range: 24–78) had received M6223 and 17 (6 male, 11 female; age range: 34–80) had received M6223 + BA. To date, 2 DLTs have been observed: 1 with 900 mg M6223 (adrenal insufficiency) and 1 with 300 mg M6223 + BA (anaemia). 8/24 (33%) pts had experienced Grade ≥3 treatment (Tx)-emergent adverse events with M6223 and 12/17 (71%) with M6223 + BA. Across all doses, M6223 serum PK were dose-proportional. Tx-driven immunophenotype changes in peripheral blood were observed, including depletion of TIGIT+ regulatory T-cells. Blood TIGIT receptor occupancy (RO) was ≥95% at the RDE of 1600 mg for the Q2W regimen. Detectable M6223-anti-drug antibodies occurred in ≈20% of treated pts with no impact on PK or RO at doses ≤900 mg. 9/24 and 2/17 pts receiving M6223 and M6223 + BA, respectively, achieved clinical benefit (stable disease at first on-Tx assessment); 3/24 and 2/17 patients, respectively, were on Tx for ≥20 weeks. M6223 ± BA had an acceptable safety profile with favourable PK and target modulation effect." @default.
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• W4295819095 date "2022-09-01" @default.
• W4295819095 modified "2023-09-27" @default.
• W4295819095 title "750P Phase I study of TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa (BA) in patients (pts) with metastatic/locally advanced solid unresectable tumours" @default.
• W4295819095 doi "https://doi.org/10.1016/j.annonc.2022.07.876" @default.
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