Ngomhlaka-26 Januwari 2025, i-Center for Drug Evaluation (CDE) ye-China National Medical Products Administration yamemezela ukuthi umjovo we-LM-108 uhloselwe ukufakwa ekwelashweni okuphumelelayo kwezimila eziqinile ezithuthukile ezine-microsatellite instability (MSI-H) noma amaphutha okulungisa okungafani (dMMR) aqhubekele phambili ngemuva kokwelashwa nge-immune checkpoint inhibitors (ICI).
I-LM-108 iyi-antibody entsha ye-Fc-optimized, anti-CCR8 monoclonal eqeda ngokukhetha ama-Tregs angena ngesimila.
Mayelana ne-CCR8:
I-CCR8 (i-chemokine receptor 8) iyilungu lomndeni ongaphansi kwe-chemokine receptor ngaphansi komndeni we-G protein-coupled receptor (GPCR). Izifundo zangaphambilini zembule ukuthi ukuvezwa kwe-CCR8 kuphansi kumaseli egazi angaphandle kanye nezicubu ezijwayelekile, kodwa kukhushulwa ikakhulukazi kuma-Tregs angena ngesimila emidlangeni eminingi yomdlavuza okuhlanganisa umdlavuza webele, umdlavuza we-colorectal, kanye nomdlavuza wamaphaphu. Ama-antibodies e-Anit-CCR8 angakhetha ukuqeda ukuncipha kwama-Tregs angena ngesimila, ngaleyo ndlela athuthukise impendulo yomzimba yokulwa nesimila futhi avimbele ukukhula kwesimila.
AUmhlangano Waminyaka Yonke we-ASCO ka-2024，Bika ukuhlaziywa okuhlanganisiwe kwemiphumela evela ezifundweni zesigaba 1/2 sesigaba sesi-3 (NCT05199753; NCT05255484; NCT05518045) ukuze kuhlolwe ukusebenza kahle nokuphepha kwe-LM-108 ngokuhlanganiswa nokwelashwa kwe-anti-PD-1 ezigulini ezinomdlavuza wesisu.
Izindlela: Iziguli ezifanelekile ezinomdlavuza wesisu ezelashwe nge-LM-108 kanye ne-antibody ye-anti-PD-1 zifakiwe ekuhlaziyweni. Iziguli zathola i-LM-108 nge-intravenous emazingeni omthamo angu-3 mg/kg Q2W, 6 mg/kg Q3W, noma 10 mg/kg Q3W kanye ne-antibody ye-anti-PD-1 (i-intravenous pembrolizumab 200 mg Q3W noma 400 mg Q6W noma i-toripalimab 240 mg Q3W). I-endpoint eyinhloko kwakuyi-ORR ehlolwe ngumcwaningi ngokwe-RECIST v1.1. I-endpoint yesibili yayihlanganisa ukuphepha, eminye imiphumela yokusebenza kahle, kanye nokuhlaziywa kwama-biomarker. Usuku lokuphela kwedatha lokuhlaziywa okuhlanganisiwe kwakunguDisemba 25, 2023.
Imiphumela: Iziguli ezingamashumi amane nesishiyagalombili ezinomdlavuza wesisu (ubudala obuphakathi: iminyaka engama-60.5; abesilisa: 72.9%) abavela eShayina, e-USA, nase-Australia belashwe ngomthamo ongu-≥ owodwa we-LM-108 kuhlanganiswe ne-pembrolizumab noma i-toripalimab. Iningi leziguli (n = 47, 97.9%) lalithole okungenani ukwelashwa okukodwa kwangaphambilini kokulwa nomdlavuza, kanti ezingu-43 (89.6%) zazithole ukwelashwa kwangaphambilini kokulwa ne-PD-1. Izehlakalo ezimbi ezihlobene nokwelashwa (ama-TRAE) zenzeka ezigulini ezingu-39 (81.3%), lapho izehlakalo ezivame kakhulu (≥15%) kwakuyi-alanine transaminase ekhuphukile (25.0%), i-aspartate transaminase ekhuphukile (22.9%), amaseli amhlophe egazi ehlile (22.9%), i-anemia (16.7%). Ama-TRAE ebanga ≥ 3 enzeke ezigulini ezingu-18 (37.5%), izehlakalo ezivame kakhulu (≥ 4%) kwakuyi-anemia (8.3%), i-lipase yanda (4.2%), ukuqubuka (4.2%), kanye nenani lama-lymphocyte lehlile (4.2%). Phakathi kweziguli ezingu-36 ezihlolwa ngempumelelo kuzo zonke izinhlobo zemithi, i-ORR yayingu-36.1% (95% CI 20.8%–53.8%) kanye ne-DCR yayingu-72.2% (95% CI 54.8%–85.8%). I-PFS ephakathi yayiyizinyanga ezingu-6.53 (95% CI 2.96–NA). Phakathi kweziguli ezingu-11 ezinesifo sazo esasiqhubekele phambili ekwelashweni kokuqala, i-ORR yayingu-63.6% (95% CI 30.8%–89.1%) kanye ne-DCR yayingu-81.8% (95% CI 48.2%–97.7%). Ezigulini eziyi-11 ezaqhubeka nokwelashwa komugqa wokuqala, eziyi-8 zazinokubonakaliswa okuphezulu kwe-CCR8. Phakathi kwalezi ziguli eziyi-8, i-ORR yayingu-87.5% kanti i-DCR yayingu-100%, kwathi i-CR eyodwa, i-PR ezi-6, kanye ne-SD eyodwa kwabonakala.
Iziphetho: I-LM-108 ehlanganiswe ne-antibody ye-anti-PD-1 ibonise umsebenzi othembisayo wokulwa nomdlavuza ezigulini ezinomdlavuza wesisu ophikisana nokwelashwa kwe-anti-PD-1. Ukwelashwa okuhlanganisiwe kwabekezelelwa kahle. Le miphumela isekela ukuhlolwa okwengeziwe kwe-LM-108 kumdlavuza wesisu one-CCR8.
Njengamanje, kusenezivivinyo eziningi zemitholampilo zobuchwepheshe obusha bokulwa nomdlavuza eShayina ezifuna iziguli. Ukubonisana ngemithi emisha kanye nobuchwepheshe, ungaxhumana noMnyango Wezizwe Ngezizwe Wesibhedlela iBeijing South Region Oncology.
Inombolo yocingo: 4008803716
Email：myimmnet@163.com
Izinkomba
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
Isikhathi sokuthunyelwe: Feb-06-2025