I te 26 o Hānuere, 2025, i panuitia e te Center for Drug Assessment (CDE) o te China National Medical Products Administration ko te werohanga LM-108 te mea hei whakauru ki te rongoā hou mō ngā pukupuku totoka matatau me te kore pumau o te microsatellite (MSI-H) me ngā hapa whakatikatika kore taurite (dMMR) kua whanake haere i muri i te maimoatanga me ngā aukati tirotiro ārai mate (ICI).
Ko te LM-108 he paturopi monoclonal anti-CCR8 hou kua arotauhia ki te Fc, e whakaiti ana i ngā Treg e uru ana ki te pukupuku.
Mō CCR8:
Ko te CCR8 (chemokine receptor 8) he mema nō te whānau chemokine receptor i raro i te whānau G protein-coupled receptor (GPCR). I whakaatuhia e ngā rangahau o mua he iti te whakaaturanga o te CCR8 i roto i ngā pūtau toto ā-taha me ngā kiko noa, engari he nui ake te whakahaere i roto i ngā Treg e uru ana ki te pukupuku i roto i ngā mate pukupuku maha tae atu ki te mate pukupuku ū, te mate pukupuku colorectal, me te mate pukupuku pūkahukahu. Ka taea e ngā paturopi Anit-CCR8 te āwhina i te whakaiti i ngā Treg e uru ana ki te pukupuku, ā, mā reira ka whakarei ake i te urupare ārai mate ārai-pukupuku me te aukati i te tipu o te pukupuku.
AHui-ā-Tau a te ASCO 2024，te ripoata i tētahi tātaritanga whakakotahi o ngā hua mai i ngā rangahau wāhanga 1/2 e 3 (NCT05199753; NCT05255484; NCT05518045) hei aromatawai i te whai huatanga me te haumaru o te LM-108 me te rongoā anti-PD-1 i roto i ngā tūroro matepukupuku puku.
Ngā Tikanga: I whakaurua ki te tātaritanga ngā tūroro whai mana me te mate pukupuku puku i rongoatia ki te LM-108 me te paturopi anti-PD-1. I whiwhi ngā tūroro i te werohanga LM-108 ā-uaua i ngā taumata horopeta o te 3 mg/kg Q2W, 6 mg/kg Q3W, 10 mg/kg Q3W rānei me te paturopi anti-PD-1 (pembrolizumab ā-uaua 200 mg Q3W, 400 mg Q6W rānei, toripalimab 240 mg Q3W rānei). Ko te pito whakamutunga tuatahi ko te ORR i aromatawaihia e te kairangahau ia RECIST v1.1. Ko ngā pito whakamutunga tuarua ko te haumaru, ngā putanga whai huatanga kē atu, me te tātaritanga tohu koiora. Ko te rā kati raraunga mō te tātaritanga whakakotahi ko te 25 o Tīhema, 2023.
Ngā Hua: E whā tekau mā waru ngā tūroro mate pukupuku puku (tau waenga: 60.5 tau; tāne: 72.9%) mai i Haina, USA, me Ahitereiria i rongoatia ≥ 1 horopeta o te LM-108 me te pembrolizumab, te toripalimab rānei. Ko te nuinga (n = 47, 97.9%) ngā tūroro i whiwhi i te iti rawa 1 maimoatanga ārai mate pukupuku o mua, ā, 43 (89.6%) i whiwhi i te rongoā ārai-PD-1 o mua. I puta ngā pānga kino e pā ana ki te maimoatanga (TRAE) i roto i te 39 (81.3%) ngā tūroro, ko ngā pānga tino noa (≥15%) ko te pikinga o te alanine transaminase (25.0%), te pikinga o te aspartate transaminase (22.9%), te hekenga o te toto toto mā (22.9%), te anemia (16.7%). I puta ngā TRAE taumata ≥ 3 i roto i te 18 (37.5%) tūroro, ko ngā mea tino kitea (≥ 4%) ko te anemia (8.3%), te pikinga o te lipase (4.2%), te ponana (4.2%), me te hekenga o te maha o ngā lymphocyte (4.2%). I roto i ngā tūroro 36 ka taea te arotake i te whai huatanga puta noa i ngā tikanga katoa, ko te ORR he 36.1% (95% CI 20.8%–53.8%) me te DCR he 72.2% (95% CI 54.8%–85.8%). Ko te PFS toharite he 6.53 marama (95% CI 2.96–NA). I roto i ngā tūroro 11 kua whanake haere te mate i runga i te maimoatanga raina tuatahi, ko te ORR he 63.6% (95% CI 30.8%–89.1%) me te DCR he 81.8% (95% CI 48.2%–97.7%). I roto i ngā tūroro 11 i ahu whakamua i runga i te maimoatanga raina tuatahi, e 8 i kitea he nui te whakaaturanga CCR8. I roto i ēnei tūroro 8, ko te ORR he 87.5%, ā, ko te DCR he 100%, me te 1 CR, 6 PR, me te 1 SD i kitea.
Ngā Whakatau: I whakaatuhia e te LM-108 i te taha o te paturopi anti-PD-1 he mahi ārai-puku pai i roto i ngā tūroro mate pukupuku puku i ātete ki te rongoā anti-PD-1. I pai te manawanui ki te rongoā whakakotahi. Ka tautokohia e ēnei hua te aromatawai anō i te LM-108 i roto i te mate pukupuku puku CCR8 pai.
I tēnei wā, he maha tonu ngā whakamātautau haumanu o ngā hangarau hou hei ārai i te matepukupuku i Haina e rapu ana i ngā tūroro. Mēnā kei te hiahia koe ki te kōrero mō ngā rongoā me ngā hangarau hou, ka taea e koe te whakapā atu ki te Tari Ao o te Hōhipera Oncology Rohe Tonga o Beijing.
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Ngā Tohutoro
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
Te wā tuku: Hui-tanguru-06-2025