Ngomhla we-13 kweyoKwindla, ngo-2025, iphephancwadi lehlabathi eliphambili iNature Medicine lapapasha uvavanyo lweMediLink's B7-H3 olujolise kwi-antibody drug conjugate (ADC) YL201 Phase 1/1b.
Uvavanyo luquke inxalenye yokunyuka kwedosi (isigaba 1) kunye nenxalenye yokwandiswa kwedosi (isigaba 1b). Izigulane ezingama-312 zizonke zibhaliswe kwiintlobo ezahlukeneyo zethumba, kuquka umhlaza wemiphunga weeseli ezincinci (ES-SCLC), umhlaza we-nasopharyngeal carcinoma (NPC), umhlaza wemiphunga weeseli ezincinci, umhlaza we-esophageal squamous cell carcinoma kunye nezinye iithumba eziqinileyo.
Phakathi kwezigulana ezingama-287 ezivavanyiweyo ukuba zisebenza kakuhle na, izinga lokuphendula elijolise ngqo (ORR) yayiyi-40.8%, kwaye izinga lokulawula isifo (DCR) yayiyi-83.6%. Ukusinda okuphakathi okungenankqubela phambili (mPFS) yayiyiinyanga ezi-5.9, kwaye ubude bexesha eliphakathi lokuphendula (mDOR) yayiyiinyanga ezi-6.3. Ukusinda okuphakathi okupheleleyo (OS) bekungavuthwanga.
Phakathi kwezigulane ezingama-48 ezine-baseline brain metastases, ezingama-21 zavavanywa; i-intracranial ORR yayiyi-28.5%; kwaye i-DOR yayiyi-6.2 iinyanga.
Zonke izigulane ezine-ES-SCLC zafumana unyango lwangaphambili nge-chemotherapy esekelwe kwiplatinum, kwaye i-95.8% yezigulane nazo zafumana unyango lwangaphambili nge-antibody ye-death 1 (PD-1) okanye i-antibody ye-death ligand 1 (PD-L1). I-ORR yayiyi-63.9%; i-DCR yayiyi-91.7%; i-mPFS yayiyi-6.3 iinyanga; kwaye i-mDOR yayiyi-5.7 iinyanga. Kwisifundo sokwanda kwedosi, izigulane ezihlanu ezine-SCLC ezafumana unyango lwangaphambili nge-topoisomerase 1 inhibitor (i-topotecan okanye i-irinotecan) zabhaliswa, kwaye isigulane esinye kuphela esaphendulayo (i-ORR, 20%). Kwizigulane ezingama-70 ezine-NPC, zonke zafumana unyango lwangaphambili nge-anti-PD-L1 kunye ne-chemotherapy esekelwe kwiplatinum, kwaye i-84.3% (59/70) yayineendlela ezimbini okanye ngaphezulu zonyango lwangaphambili lwenkqubo. Izigulane ezibini ezine-NPC zifumene impendulo epheleleyo (CR), zine-ORR engama-48.6% kunye ne-DCR engama-92.9%. I-mPFS ibiziinyanga eziyi-7.8, kwaye i-mDOR ibiziinyanga eziyi-8.4. Izigulane ezingama-64 ezine-wild-type NSCLC zivavanyiwe, kuquka ezingama-28 ezine-adenocarcinoma, ezili-12 ezine-squamous cell carcinoma kunye nezingama-24 ezine-lymphoepithelioma-like carcinoma (LELC). Zizonke, i-90.6% (58/64) yezigulane ezine-NSCLC zafumana unyango lwangaphambili nge-anti-PD-L1 kunye ne-platinum-based chemotherapy. Amaxabiso e-ORR kwizigulane ezine-lung adenocarcinoma, i-squamous cell carcinoma kunye ne-LELC yayingama-28.6%, 8.3% kunye nama-54.2%, ngokwahlukeneyo, kwaye i-mDOR ibiziinyanga ezili-13.6, iinyanga ezi-2.6 kunye neenyanga eziyi-6.7, ngokwahlukeneyo.
I-YL201 ibonakalise iprofayili yokhuseleko eyamkelekileyo kunye nokusebenza okuthembisayo kwizigulana ezinyangwe kakhulu ngaphambi kokuba zifumane iithumba eziqinileyo, ngakumbi kwabo bane-ES-SCLC, NPC okanye i-lymphoepithelioma-like carcinoma.
I-YL201 yi-ADC entsha equlathe i-antibody ye-anti-B7H3 monoclonal yabantu edityaniswe ne-topoisomerase 1 inhibitor entsha nge-linker eqhekekayo ye-protease, enomlinganiselo we-drug-to-antibody we-8. I-YL201 yaphuhliswa kusetyenziswa iqonga le-MediLink's tumor microenvironment activable linker-payload (TMALIN), elibonakaliswa yi-linker-payload ephilic kakhulu, uzinzo oluphawulekayo ekujikelezeni kwegazi kunye nendlela yokukhulula i-payload ephindwe kabini equka ukuqhekeka kokubini ngaphandle kwendawo kwi-tumor microenvironment nangaphakathi kwi-lysosomes. Kwisifundo sangaphambi kweklinikhi, i-YL201 ibonise umsebenzi onamandla wokulwa ne-tumor kwiimodeli ezahlukeneyo zegundane ze-CDX/PDX ezine-SCLC, NSCLC, umhlaza we-esophageal kunye nomhlaza we-ovarian. Idatha yokusebenza kakuhle kunye nokhuseleko oluvela kolu phononongo lwangaphambi kweklinikhi lubonisa ibhalansi elungileyo yenzuzo-yomngcipheko, exhasa uphuhliso olongezelelweyo lwe-YL201 kwiklinikhi.
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.
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Email：myimmnet@163.com
Ixesha leposi: Epreli-08-2025