Thaum Lub Ib Hlis 26, 2025, Lub Chaw Saib Xyuas Kev Tshuaj Xyuas Tshuaj (CDE) ntawm Tuam Tshoj Lub Chaw Tswj Xyuas Khoom Siv Kho Mob tau tshaj tawm tias LM-108 txhaj tshuaj yog npaj yuav suav nrog hauv kev kho mob tshiab rau cov qog nqaij hlav khov kho nrog microsatellite instability (MSI-H) lossis mismatch repair defects (dMMR) uas tau nce qib tom qab kev kho mob nrog cov tshuaj tiv thaiv kab mob (ICI).
LM-108 yog ib qho tshuaj tiv thaiv kab mob monoclonal tshiab uas tau kho kom zoo dua qub, uas xaiv cov tshuaj Tregs uas nkag mus rau hauv cov qog nqaij hlav.
Txog CCR8:
CCR8 (chemokine receptor 8) yog ib tug tswv cuab ntawm chemokine receptor subfamily nyob rau hauv G protein-coupled receptor (GPCR) tsev neeg. Cov kev tshawb fawb yav dhau los tau qhia tias qhov kev qhia tawm ntawm CCR8 yog qis hauv cov qe ntshav peripheral thiab cov nqaij ib txwm muaj, tab sis tshwj xeeb tshaj yog upregulated hauv tumor-infiltrating Tregs hauv ntau yam mob qog noj ntshav suav nrog mob qog noj ntshav mis, mob qog noj ntshav colorectal, thiab mob qog noj ntshav ntsws. Anit-CCR8 antibodies tuaj yeem xaiv qhov nruab nrab ntawm kev txo qis ntawm tumor-infiltrating Tregs, yog li txhim kho cov lus teb tiv thaiv kab mob qog noj ntshav thiab tiv thaiv kev loj hlob ntawm qog noj ntshav.
ALub Rooj Sib Tham Txhua Xyoo ASCO Xyoo 2024,tshaj tawm kev tshuaj xyuas ua ke ntawm cov txiaj ntsig los ntawm 3 theem 1/2 kev tshawb fawb (NCT05199753; NCT05255484; NCT05518045) los ntsuas qhov ua tau zoo thiab kev nyab xeeb ntawm LM-108 ua ke nrog kev kho mob anti-PD-1 rau cov neeg mob uas muaj mob qog noj ntshav hauv plab.
Cov Txheej Txheem: Cov neeg mob uas tsim nyog uas muaj mob qog noj ntshav hauv plab tau kho nrog LM-108 ua ke nrog cov tshuaj tiv thaiv anti-PD-1 tau suav nrog hauv kev tshuaj xyuas. Cov neeg mob tau txais LM-108 txhaj rau hauv cov hlab ntsha ntawm cov koob tshuaj ntawm 3 mg / kg Q2W, 6 mg / kg Q3W, lossis 10 mg / kg Q3W ntxiv rau cov tshuaj tiv thaiv anti-PD-1 (tso rau hauv cov hlab ntsha pembrolizumab 200 mg Q3W lossis 400 mg Q6W lossis toripalimab 240 mg Q3W). Lub ntsiab lus tseem ceeb yog ORR uas tus kws tshawb fawb ntsuas ib RECIST v1.1. Lub ntsiab lus thib ob suav nrog kev nyab xeeb, lwm yam txiaj ntsig zoo, thiab kev tshuaj xyuas biomarkers. Hnub kawg rau kev tshuaj xyuas ua ke yog Lub Kaum Ob Hlis 25, 2023.
Cov Txiaj Ntsig: Plaub caug yim tus neeg mob uas muaj mob qog noj ntshav hauv plab (hnub nyoog nruab nrab: 60.5 xyoo; txiv neej: 72.9%) los ntawm Tuam Tshoj, Tebchaws Meskas, thiab Australia tau kho ≥ 1 koob tshuaj ntawm LM-108 ua ke nrog pembrolizumab lossis toripalimab. Feem ntau (n = 47, 97.9%) cov neeg mob tau txais tsawg kawg 1 kev kho mob qog noj ntshav ua ntej, thiab 43 (89.6%) tau txais kev kho mob anti-PD-1 ua ntej. Cov teeb meem tsis zoo ntsig txog kev kho mob (TRAEs) tau tshwm sim hauv 39 (81.3%) cov neeg mob, uas cov teeb meem feem ntau (≥15%) yog alanine transaminase nce (25.0%), aspartate transaminase nce (22.9%), cov qe ntshav dawb txo qis (22.9%), ntshav tsis txaus (16.7%). Qib ≥ 3 TRAEs tau tshwm sim rau 18 tus neeg mob (37.5%), cov xwm txheej feem ntau (≥ 4%) yog ntshav tsis txaus (8.3%), lipase nce (4.2%), pob khaus (4.2%), thiab cov lej lymphocyte txo qis (4.2%). Ntawm 36 tus neeg mob uas ntsuas tau qhov ua tau zoo thoob plaws txhua txoj kev kho mob, ORR yog 36.1% (95% CI 20.8%–53.8%) thiab DCR yog 72.2% (95% CI 54.8%–85.8%). Qhov nruab nrab PFS yog 6.53 lub hlis (95% CI 2.96–NA). Ntawm 11 tus neeg mob uas tus kab mob tau nce qib ntawm kev kho mob thawj kab, ORR yog 63.6% (95% CI 30.8%–89.1%) thiab DCR yog 81.8% (95% CI 48.2%–97.7%). Ntawm 11 tus neeg mob uas tau nce qib ntawm kev kho mob thawj kab, 8 muaj CCR8 kev qhia siab. Ntawm 8 tus neeg mob no, ORR yog 87.5% thiab DCR yog 100%, nrog 1 CR, 6 PR, thiab 1 SD pom.
Xaus Lus: LM-108 ua ke nrog cov tshuaj tiv thaiv kab mob anti-PD-1 tau qhia txog kev ua haujlwm tiv thaiv kab mob qog nqaij hlav hauv cov neeg mob uas muaj mob qog nqaij hlav hauv plab uas tsis kam rau kev kho mob anti-PD-1. Kev kho mob ua ke tau zoo. Cov txiaj ntsig no txhawb nqa kev soj ntsuam ntxiv ntawm LM-108 hauv CCR8 mob qog nqaij hlav hauv plab.
Tam sim no, tseem muaj ntau qhov kev sim tshuaj kho mob qog noj ntshav tshiab hauv Suav teb nrhiav cov neeg mob. Kev sab laj txog cov tshuaj tshiab thiab cov thev naus laus zis, koj tuaj yeem tiv tauj Beijing South Region Oncology Hospital International Department.
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Cov ntaub ntawv siv los ua piv txwv
1.https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
2.https://www.lanovamedicines.com/en
3.https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2504
Lub sijhawm tshaj tawm: Lub Ob Hlis-06-2025