Pa 13 Marichi, 2025, magazini yapamwamba yapadziko lonse ya Nature Medicine inafalitsa mayeso a MediLink a B7-H3 okhudzana ndi mankhwala ophera ma antibodies (ADC) YL201 Phase 1/1b.
Kuyesaku kunaphatikizapo gawo lokulitsa mlingo (gawo 1) ndi gawo lokulitsa mlingo (gawo 1b). Odwala onse 312 adalembetsedwa m'mitundu yosiyanasiyana ya chotupa, kuphatikizapo khansa ya m'mapapo ya maselo ang'onoang'ono (ES-SCLC), khansa ya m'mphuno (NPC), khansa ya m'mapapo ya maselo ang'onoang'ono, khansa ya m'mimba ya squamous cell ndi zotupa zina zolimba.
Pakati pa odwala 287 omwe adayesedwa kuti agwire bwino ntchito, chiŵerengero cha yankho lolunjika (ORR) chinali 40.8%, ndipo chiŵerengero chowongolera matenda (DCR) chinali 83.6%. Kupulumuka kwapakati popanda kupita patsogolo (mPFS) kunali miyezi 5.9, ndipo nthawi yapakati yoyankha (mDOR) inali miyezi 6.3. Kupulumuka kwapakati konse (OS) sikunali kokhwima.
Mwa odwala 48 omwe anali ndi matenda a ubongo, 21 anayesedwa; ORR ya mkati mwa mutu inali 28.5%; ndipo DOR inali miyezi 6.2.
Odwala onse omwe ali ndi ES-SCLC adalandira chithandizo chamankhwala cha platinum-based chemotherapy kale, ndipo 95.8% ya odwala adalandiranso chithandizo chamankhwala cha death 1 (PD-1) kapena antibody ya death ligand 1 (PD-L1). ORR inali 63.9%; DCR inali 91.7%; mPFS inali miyezi 6.3; ndipo mDOR inali miyezi 5.7. Mu kafukufuku wokhudza kuchuluka kwa mlingo, odwala asanu omwe ali ndi SCLC omwe adalandira chithandizo chamankhwala cha topoisomerase 1 inhibitor (topotecan kapena irinotecan) adalembedwa, ndipo wodwala m'modzi yekha adayankha (ORR, 20%). Mwa odwala 70 omwe anali ndi NPC, onse adalandira chithandizo chamankhwala cha anti-PD-L1 ndi platinum-based chemotherapy kale, ndipo 84.3% (59/70) anali ndi njira ziwiri kapena zingapo zochiritsira zam'mbuyomu. Odwala awiri omwe anali ndi NPC adapeza yankho lathunthu (CR), ndi ORR ya 48.6% ndi DCR ya 92.9%. MPFS inali miyezi 7.8, ndipo mDOR inali miyezi 8.4. Odwala onse 64 omwe anali ndi NSCLC yamtundu wa wild-type adayesedwa, kuphatikiza 28 omwe anali ndi adenocarcinoma, 12 omwe anali ndi squamous cell carcinoma ndi 24 omwe anali ndi lymphoepithelioma-like carcinoma (LELC). Onse, 90.6% (58/64) ya odwala omwe ali ndi NSCLC adalandira chithandizo chamankhwala chotsutsana ndi PD-L1 ndi platinum-based chemotherapy. Ma ORR a odwala omwe ali ndi lung adenocarcinoma, squamous cell carcinoma ndi LELC anali 28.6%, 8.3% ndi 54.2%, motsatana, ndipo mDOR inali miyezi 13.6, miyezi 2.6 ndi miyezi 6.7, motsatana.
YL201 yawonetsa chitetezo chovomerezeka komanso yothandiza kwambiri kwa odwala omwe adachiritsidwa kale omwe ali ndi zotupa zolimba kwambiri, makamaka kwa iwo omwe ali ndi ES-SCLC, NPC kapena lymphoepithelioma-like carcinoma.
YL201 ndi ADC yatsopano yokhala ndi antibody ya monoclonal ya munthu yolumikizidwa ku choletsa chatsopano cha topoisomerase 1 kudzera mu cholumikizira cholumikizira cha protease, chokhala ndi chiŵerengero cha mankhwala-kwa-antibody cha 8. YL201 idapangidwa pogwiritsa ntchito nsanja ya MediLink's tumor microenvironment activable linker-payload (TMALIN), yomwe imadziwika ndi linker-payload yochuluka kwambiri, kukhazikika kodabwitsa mu kayendedwe ka magazi ndi njira yotulutsira payload iwiri yomwe imaphatikizapo kusweka kwakunja kwa chotupa komanso mkati mwa maselo mkati mwa lysosomes. Mu kafukufuku woyambirira, YL201 idawonetsa mphamvu yolimbana ndi chotupa m'mitundu yosiyanasiyana ya mbewa za CDX/PDX ndi SCLC, NSCLC, khansa ya m'mero ndi khansa ya ovari. Deta yogwira ntchito komanso chitetezo kuchokera ku kafukufuku woyambirira uyu ikuwonetsa kuti pali phindu labwino pakati pa chiopsezo, zomwe zimathandiza kuti YL201 ipitirire kukula mchipatala.
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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Nthawi yotumizira: Epulo-08-2025