Pa Januwale 26, 2025, Center for Drug Evaluation (CDE) ya China National Medical Products Administration idalengeza kuti jakisoni wa LM-108 cholinga chake ndikuphatikizidwa mu chithandizo chamankhwala cha zotupa zolimba zomwe zili ndi kusakhazikika kwa microsatellite (MSI-H) kapena zolakwika zokonzanso zolakwika (dMMR) zomwe zapita patsogolo pambuyo pa chithandizo ndi zoletsa zoletsa chitetezo chamthupi (ICI).
LM-108 ndi antibody yatsopano ya Fc-optimized, anti-CCR8 monoclonal antibody yomwe imachotsa Tregs zomwe zimalowa m'thupi.
Zokhudza CCR8:
CCR8 (chemokine receptor 8) ndi membala wa gulu la chemokine receptor lomwe lili pansi pa banja la G protein-coupled receptor (GPCR). Kafukufuku wakale adawonetsa kuti CCR8 imapezeka m'maselo ochepa a m'magazi ndi minofu yabwinobwino, koma imawonjezeka makamaka m'matenda olowa m'mimba mwa khansa zosiyanasiyana kuphatikizapo khansa ya m'mawere, khansa ya m'matumbo, ndi khansa ya m'mapapo. Ma antibodies a Anit-CCR8 amatha kuletsa kuchepa kwa ma Tregs olowa m'mimba mwa khansa, motero kukulitsa chitetezo cha mthupi chotsutsana ndi chotupa ndikuletsa kukula kwa chotupa.
AMsonkhano Wapachaka wa ASCO wa 2024，Nenani za kusanthula kophatikizana kwa zotsatira kuchokera ku maphunziro atatu a gawo 1/2 (NCT05199753; NCT05255484; NCT05518045) kuti muwone momwe LM-108 imagwirira ntchito komanso chitetezo chake pamodzi ndi mankhwala oletsa PD-1 mwa odwala omwe ali ndi khansa ya m'mimba.
Njira: Odwala oyenerera omwe ali ndi khansa ya m'mimba omwe adalandira chithandizo cha LM-108 pamodzi ndi anti-PD-1 antibody adaphatikizidwa mu kusanthulaku. Odwala adalandira LM-108 kudzera m'mitsempha pamlingo wa 3 mg/kg Q2W, 6 mg/kg Q3W, kapena 10 mg/kg Q3W kuphatikiza anti-PD-1 antibody (intravenous pembrolizumab 200 mg Q3W kapena 400 mg Q6W kapena toripalimab 240 mg Q3W). Mapeto oyamba anali ORR yowunikidwa ndi ofufuza pa RECIST v1.1. Mapeto achiwiri adaphatikizapo chitetezo, zotsatira zina zogwira ntchito, ndi kusanthula kwa biomarkers. Tsiku lomaliza la kusanthula komwe kwaphatikizidwa linali Disembala 25, 2023.
Zotsatira: Odwala 48 omwe ali ndi khansa ya m'mimba (zaka zapakati: zaka 60.5; amuna: 72.9%) ochokera ku China, USA, ndi Australia adapatsidwa chithandizo cha ≥ mlingo umodzi wa LM-108 pamodzi ndi pembrolizumab kapena toripalimab. Odwala ambiri (n = 47, 97.9%) adalandira chithandizo chimodzi chotsutsana ndi khansa m'mbuyomu, ndipo 43 (89.6%) adalandira chithandizo cha anti-PD-1 m'mbuyomu. Zochitika zoyipa zokhudzana ndi chithandizo (TRAEs) zidachitika mwa odwala 39 (81.3%), pomwe zochitika zodziwika kwambiri (≥15%) zinali kuwonjezeka kwa alanine transaminase (25.0%), kuwonjezeka kwa aspartate transaminase (22.9%), kuchepa kwa maselo oyera m'magazi (22.9%), kuchepa kwa magazi m'thupi (16.7%). Ma TRAE a Giredi ≥ 3 adachitika mwa odwala 18 (37.5%), zochitika zodziwika kwambiri (≥ 4%) zinali kuchepa kwa magazi m'thupi (8.3%), kuchuluka kwa lipase (4.2%), ziphuphu (4.2%), ndi kuchuluka kwa ma lymphocyte kudatsika (4.2%). Pakati pa odwala 36 omwe adayesedwa bwino pamankhwala onse, ORR inali 36.1% (95% CI 20.8%–53.8%) ndipo DCR inali 72.2% (95% CI 54.8%–85.8%). PFS yapakati inali miyezi 6.53 (95% CI 2.96–NA). Pakati pa odwala 11 omwe matenda awo adapita patsogolo pa chithandizo choyamba, ORR inali 63.6% (95% CI 30.8%–89.1%) ndipo DCR inali 81.8% (95% CI 48.2%–97.7%). Mwa odwala 11 omwe adapita patsogolo ndi chithandizo choyamba, 8 anali ndi CCR8 yochuluka. Pakati pa odwala 8 awa, ORR inali 87.5% ndipo DCR inali 100%, ndipo CR imodzi, 6 PR, ndi SD imodzi zinawonedwa.
Mapeto: LM-108 pamodzi ndi antibody yotsutsana ndi PD-1 inasonyeza kuti imagwira ntchito bwino polimbana ndi chotupa mwa odwala khansa ya m'mimba yomwe inali yotsutsana ndi mankhwala otsutsana ndi PD-1. Mankhwala ophatikizanawo analoledwa bwino. Zotsatirazi zikuthandizira kuwunikanso kwa LM-108 mu khansa ya m'mimba ya CCR8.
Pakadali pano, pali mayesero ambiri azachipatala a ukadaulo watsopano wothana ndi khansa ku China omwe akufuna odwala. Mukafunsira mankhwala ndi ukadaulo watsopano, mutha kulumikizana ndi Dipatimenti Yapadziko Lonse ya Chipatala cha Oncology ku Beijing South Region.
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Email：myimmnet@163.com
Zolemba
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
Nthawi yotumizira: Feb-06-2025