Ma Malaki 13, 2025, ua paʻi ka puke pai honua kiʻekiʻe ʻo Nature Medicine i ka hoʻokolohua B7-H3 targeting antibody drug conjugate (ADC) YL201 Phase 1/1b a MediLink.
Ua komo pū ka hoʻokolohua i kahi ʻāpana hoʻonui lāʻau (pae 1) a me kahi ʻāpana hoʻonui lāʻau (pae 1b). Ua kākau inoa ʻia he 312 mau maʻi ma nā ʻano puʻupuʻu like ʻole, me ka maʻi kanesa māmā liʻiliʻi ākea (ES-SCLC), ka carcinoma nasopharyngeal (NPC), ka maʻi kanesa māmā ʻaʻole liʻiliʻi, ka carcinoma cell squamous esophageal a me nā puʻupuʻu paʻa ʻē aʻe.
Ma waena o nā maʻi 287 i hiki ke loiloi ʻia no ka pono, ʻo ka helu pane pahuhopu (ORR) he 40.8%, a ʻo ka helu kaohi maʻi (DCR) he 83.6%. ʻO ke ola waena median progression-free (mPFS) he 5.9 mahina, a ʻo ka lōʻihi waena o ka pane (mDOR) he 6.3 mahina. ʻAʻole i oʻo ka awelika holoʻokoʻa holoʻokoʻa (OS).
Ma waena o nā maʻi 48 me nā metastases o ka lolo baseline, 21 i hiki ke loiloi ʻia; ʻo ka intracranial ORR he 28.5%; a ʻo ka DOR he 6.2 mahina.
Ua loaʻa i nā maʻi āpau me ES-SCLC ka lāʻau lapaʻau mua me ka chemotherapy platinum-based, a 95.8% o nā maʻi i loaʻa pū kekahi lāʻau lapaʻau mua me ka programmed death 1 (PD-1) a i ʻole programmed death ligand 1 (PD-L1) antibody. ʻO 63.9% ka ORR; ʻo 91.7% ka DCR; ʻo 6.3 mahina ka mPFS; a ʻo 5.7 mahina ka mDOR. I loko o ke aʻo ʻana i ka dose-escalation, ʻelima mau maʻi me SCLC i loaʻa ka lāʻau lapaʻau mua me kahi topoisomerase 1 inhibitor (topotecan a irinotecan paha), me hoʻokahi wale nō maʻi i pane mai (ORR, 20%). No nā maʻi 70 me NPC, ua loaʻa i nā mea āpau ka lāʻau lapaʻau mua me ka anti-PD-L1 a me ka chemotherapy platinum-based, a ʻo 84.3% (59/70) he ʻelua a ʻoi aku paha nā laina o nā lāʻau lapaʻau systemic mua. ʻElua o nā maʻi me NPC i loaʻa kahi pane piha (CR), me ka ORR o 48.6% a me ka DCR o 92.9%. ʻO 7.8 mahina ka mPFS, a ʻo 8.4 mahina ka mDOR. Ua loiloi ʻia he 64 mau maʻi me ka NSCLC ʻano hihiu, me 28 me ka adenocarcinoma, 12 me ka squamous cell carcinoma a me 24 me ka lymphoepithelioma-like carcinoma (LELC). Ma ka huina, 90.6% (58/64) o nā maʻi me NSCLC i loaʻa mua ka lāʻau lapaʻau me ka anti-PD-L1 a me ka chemotherapy platinum-based. ʻO nā waiwai ORR no nā maʻi me ka adenocarcinoma māmā, squamous cell carcinoma a me LELC he 28.6%, 8.3% a me 54.2%, kēlā me kēia, a ʻo ka mDOR he 13.6 mahina, 2.6 mahina a me 6.7 mahina, kēlā me kēia.
Ua hōʻike ʻo YL201 i kahi ʻano palekana i ʻae ʻia a me kahi hopena maikaʻi i nā poʻe maʻi i mālama mua ʻia me nā ʻōpū paʻa paʻa kiʻekiʻe, ʻoi aku hoʻi i ka poʻe me ES-SCLC, NPC a i ʻole lymphoepithelioma-like carcinoma.
ʻO YL201 kahi ADC hou i loaʻa kahi antibody monoclonal anti-B7H3 kanaka i hoʻohui ʻia i kahi mea hoʻopaʻa topoisomerase 1 hou ma o kahi mea hoʻopili protease-cleavable, me ka lākiō lāʻau-i-antibody o 8. Ua hoʻomohala ʻia ʻo YL201 me ka hoʻohana ʻana i ka paepae linker-payload activable linker-payload (TMALIN) o MediLink, kahi i hōʻike ʻia e kahi linker-payload hydrophilic kiʻekiʻe, ke kūpaʻa kupaianaha i ke kahe ʻana a me kahi ʻano hoʻokuʻu payload pālua e komo pū ana me ka cleavage ma waho o ka microenvironment tumor a ma loko o ka lysosomes. Ma kahi noiʻi preclinical, ua hōʻike ʻo YL201 i ka hana anti-tumor ikaika i nā ʻano hiʻohiʻona ʻiole CDX/PDX like ʻole me SCLC, NSCLC, ka maʻi ʻaʻai esophageal a me ka maʻi ʻaʻai ovarian. Hōʻike ka ʻikepili pono a me ka palekana mai kēia noiʻi preclinical i kahi kaulike maikaʻi-pilikia, e kākoʻo ana i ka hoʻomohala hou ʻana o YL201 ma ke keʻena lapaʻau.
I kēia manawa, nui nā hoʻokolohua lapaʻau o nā ʻenehana anti-cancer hou ma Kina e ʻimi nei i nā maʻi. I ke kūkākūkā ʻana i nā lāʻau lapaʻau a me nā ʻenehana hou, hiki iā ʻoe ke hoʻokaʻaʻike aku i ka Beijing South Region Oncology Hospital International Department.
Helu Kelepona：4008803716
Email：myimmnet@163.com
Ka manawa hoʻouna: ʻApelila-08-2025