Ngomhla wama-26 kweyoMqungu, ngowama-2025, iZiko loVavanyo lwaMayeza (i-CDE) le-China National Medical Products Administration labhengeza ukuba i-LM-108 injection yenzelwe ukubandakanywa kunyango oluphambili lwee-tumor eziqinileyo eziphucukileyo ezine-microsatellite instability (MSI-H) okanye iziphene zokulungisa ukungalingani (dMMR) eziye zaqhubeka emva konyango nge-immune checkpoint inhibitors (ICI).
I-LM-108 yi-antibody entsha ye-Fc-optimized, i-anti-CCR8 monoclonal antibody ekhethayo ukunciphisa ii-Tregs ezifaka iithumba.
Malunga neCCR8:
I-CCR8 (i-chemokine receptor 8) lilungu le-subfamily ye-chemokine receptor phantsi kosapho lwe-G protein-coupled receptor (GPCR). Izifundo zangaphambili zityhile ukuba ukubonakaliswa kwe-CCR8 kuphantsi kwiiseli zegazi ezingaphandle kunye nezicubu eziqhelekileyo, kodwa kunyuswa ngokukodwa kwi-Tregs ezifaka i-tumor kwimihlaza emininzi kubandakanya umhlaza webele, umhlaza we-colorectal, kunye nomhlaza wemiphunga. Ii-antibodies ze-Anit-CCR8 zinokukhetha ukuphelisa i-Tregs ezifaka i-tumor, ngaloo ndlela ziphucula impendulo yomzimba yokulwa ne-tumor kwaye zithintele ukukhula kwe-tumor.
AIntlanganiso Yonyaka ye-ASCO ka-2024，Ingxelo yohlalutyo oludibeneyo lweziphumo ezivela kwizifundo zesigaba 1/2 sesigaba esi-3 (NCT05199753; NCT05255484; NCT05518045) ukuvavanya ukusebenza kakuhle kunye nokhuseleko lwe-LM-108 xa idibene nonyango lwe-anti-PD-1 kwizigulane ezinomhlaza wesisu.
Iindlela: Izigulana ezifanelekileyo ezinomhlaza wesisu ezinyangwe nge-LM-108 kunye ne-anti-PD-1 antibody zibandakanyiwe kuhlalutyo. Izigulana zifumene i-LM-108 ngemithambo kumanqanaba edosi ye-3 mg/kg Q2W, 6 mg/kg Q3W, okanye 10 mg/kg Q3W kunye ne-anti-PD-1 antibody (i-intravenous pembrolizumab 200 mg Q3W okanye 400 mg Q6W okanye i-toripalimab 240 mg Q3W). Isiphelo esiphambili yayiyi-ORR evavanyiweyo ngumphandi ngokwe-RECIST v1.1. Isiphelo sesibini siquka ukhuseleko, ezinye iziphumo zokusebenza kakuhle, kunye nohlalutyo lwee-biomarkers. Umhla wokugqibela wedatha yohlalutyo oludibeneyo yayinguDisemba 25, 2023.
Iziphumo: Izigulane ezingamashumi amane anesibhozo ezinomhlaza wesisu (ubudala obuphakathi: iminyaka engama-60.5; amadoda: 72.9%) ezivela eTshayina, eMelika, nase-Australia zinyangwe nge-≥ idosi enye ye-LM-108 kunye ne-pembrolizumab okanye i-toripalimab. Uninzi lwezigulane (n = 47, 97.9%) zazifumene ubuncinane unyango olunye lwangaphambili lokulwa nomhlaza, kwaye ezingama-43 (89.6%) zazifumene unyango lwangaphambili lwe-anti-PD-1. Iziganeko ezimbi ezinxulumene nonyango (ii-TRAE) zenzeka kwizigulane ezingama-39 (81.3%), apho iziganeko eziqhelekileyo (≥15%) yayikukwanda kwe-alanine transaminase (25.0%), ukwanda kwe-aspartate transaminase (22.9%), ukuncipha kweeseli ezimhlophe zegazi (22.9%), i-anemia (16.7%). Ii-TRAE zeBanga ≥ 3 zenzeke kwizigulane ezili-18 (37.5%), ezona ziganeko zixhaphakileyo (≥ 4%) yayiyi-anemia (8.3%), i-lipase yanda (4.2%), irhashalala (4.2%), kunye nenani le-lymphocyte lehlile (4.2%). Phakathi kwezigulane ezingama-36 ezivavanywayo ngempumelelo kuzo zonke iindlela zonyango, i-ORR yayiyi-36.1% (95% CI 20.8%–53.8%) kwaye i-DCR yayiyi-72.2% (95% CI 54.8%–85.8%). I-PFS ephakathi yayiyiinyanga eziyi-6.53 (95% CI 2.96–NA). Phakathi kwezigulane ezili-11 ezisifo sazo saqhubeka kunyango lokuqala, i-ORR yayiyi-63.6% (95% CI 30.8%–89.1%) kwaye i-DCR yayiyi-81.8% (95% CI 48.2%–97.7%). Kwizigulane ezili-11 ezaqhubeka nonyango lokuqala, ezisi-8 zazine-CCR8 ephezulu. Phakathi kwezi zigulane zisi-8, i-ORR yayiyi-87.5% kwaye i-DCR yayiyi-100%, kwaye kwabonwa i-CR e-1, i-PR ezi-6, kunye ne-SD e-1.
Izigqibo: I-LM-108 xa idibene ne-antibody ye-anti-PD-1 ibonise umsebenzi othembisayo wokulwa nethumba kwizigulana ezinomhlaza wesisu owawungamelani nonyango lwe-anti-PD-1. Unyango oludibeneyo lwanyanyezelwa kakuhle. Ezi ziphumo zixhasa uvavanyo olongezelelekileyo lwe-LM-108 kumhlaza wesisu one-CCR8.
Okwangoku, kusekho iimvavanyo ezininzi zeklinikhi zobuchwepheshe obutsha bokulwa nomhlaza eTshayina obufuna izigulane. Iingcebiso ngamayeza amatsha kunye nobuchwepheshe, ungaqhagamshelana neSebe leMicimbi yeZibhedlele ze-Oncology zaseBeijing South Region.
Inombolo yefowuni: 4008803716
Email：myimmnet@163.com
Iireferensi
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
Ixesha leposi: Feb-06-2025