NgoMashi 13, 2025, iphephandaba lamazwe ngamazwe i-Nature Medicine lashicilela isivivinyo se-MediLink se-B7-H3 esiqondisa i-antibody drug conjugate (ADC) YL201 Phase 1/1b.
Ukuhlolwa kwakuhlanganisa ingxenye yokwanda komthamo (isigaba 1) kanye nengxenye yokwandiswa komthamo (isigaba 1b). Iziguli ezingu-312 zibhaliswe ezinhlotsheni eziningi zezimila, okuhlanganisa umdlavuza wamaphaphu wamaseli amancane (ES-SCLC), i-nasopharyngeal carcinoma (NPC), umdlavuza wamaphaphu wamaseli amancane, i-esophageal squamous cell carcinoma kanye nezinye izimila eziqinile.
Phakathi kweziguli ezingu-287 ezihlolwe ukusebenza kahle, izinga lokuphendula eliqondile (ORR) lalingu-40.8%, kanti izinga lokulawula isifo (DCR) lalingu-83.6%. Ukusinda okuphakathi okungenalo ukuqhubekela phambili (mPFS) kwakuyizinyanga ezingu-5.9, kanti ubude obuphakathi bokuphendula (mDOR) kwakuyizinyanga ezingu-6.3. Ukusinda okuphakathi okuvamile (OS) kwakungavuthiwe.
Phakathi kweziguli ezingu-48 ezine-baseline brain metastases, ezingu-21 zahlolwa; i-intracranial ORR yayingu-28.5%; kanti i-DOR yayiyizinyanga ezingu-6.2.
Zonke iziguli ezine-ES-SCLC zathola ukwelashwa kwangaphambilini nge-chemotherapy esekelwe eplatinum, kanti u-95.8% weziguli nazo zathola ukwelashwa kwangaphambilini nge-antibody yokufa 1 (PD-1) noma i-antibody yokufa 1 (PD-L1) ehlelwe. I-ORR yayingu-63.9%; i-DCR yayingu-91.7%; i-mPFS yayiyizinyanga ezingu-6.3; kanti i-mDOR yayiyizinyanga ezingu-5.7. Esifundweni sokwanda komthamo, iziguli ezinhlanu ezine-SCLC ezathola ukwelashwa kwangaphambilini nge-topoisomerase 1 inhibitor (i-topotecan noma i-irinotecan) zabhaliswa, kanti isiguli esisodwa kuphela esaphendula (i-ORR, 20%). Kulezi ziguli ezingu-70 ezine-NPC, zonke zathola ukwelashwa kwangaphambilini nge-anti-PD-L1 kanye ne-chemotherapy esekelwe eplatinum, kanti u-84.3% (59/70) wayenezindlela ezimbili noma ngaphezulu zokwelapha okuhleliwe kwangaphambilini. Iziguli ezimbili ezine-NPC zithole impendulo ephelele (CR), zine-ORR engu-48.6% kanye ne-DCR engu-92.9%. I-mPFS yayinezinyanga ezingu-7.8, kanti i-mDOR yayiyizinyanga ezingu-8.4. Iziguli ezingu-64 ezine-wild-type NSCLC zahlolwa, okuhlanganisa ezingu-28 ezine-adenocarcinoma, ezingu-12 ezine-squamous cell carcinoma kanye nezingu-24 ezine-lymphoepithelioma-like carcinoma (LELC). Sekukonke, u-90.6% (58/64) weziguli ezine-NSCLC wayenokwelashwa kwangaphambilini nge-anti-PD-L1 kanye ne-platinum-based chemotherapy. Amanani e-ORR ezigulini ezine-lung adenocarcinoma, i-squamous cell carcinoma kanye ne-LELC ayengu-28.6%, 8.3% kanye no-54.2%, ngokulandelana, kanti i-mDOR yayinezinyanga ezingu-13.6, izinyanga ezingu-2.6 kanye nezinyanga ezingu-6.7, ngokulandelana.
I-YL201 ibonise iphrofayili yokuphepha eyamukelekayo kanye nokusebenza kahle okuthembisayo ezigulini ezelashwe kakhulu ngaphambi kwesikhathi ezinezimila eziqinile ezithuthukile, ikakhulukazi kulabo abane-ES-SCLC, NPC noma i-lymphoepithelioma-like carcinoma.
I-YL201 iyi-ADC entsha equkethe i-antibody yomuntu elwa ne-B7H3 monoclonal ehlanganiswe ne-inhibitor entsha ye-topoisomerase 1 nge-linker ehlukanisayo ye-protease, enesilinganiso se-drug-to-antibody esingu-8. I-YL201 yathuthukiswa kusetshenziswa ipulatifomu ye-MediLink's tumor microenvironment activable linker-payload (TMALIN), ebonakala nge-linker-payload ephakelayo emanzini amaningi, ukuzinza okuphawulekayo ekujikelezeni kwegazi kanye nendlela yokukhulula i-payload ekabili ehlanganisa ukuqhekeka kokubili ngaphandle kwesikhumba endaweni encane ye-tumor kanye nangaphakathi kweseli ngaphakathi kwe-lysosomes. Esifundweni sangaphambi kwe-clinical, i-YL201 ibonise umsebenzi onamandla wokulwa ne-tumor kumamodeli ahlukahlukene egundane le-CDX/PDX ane-SCLC, NSCLC, umdlavuza we-esophageal kanye nomdlavuza wesibeletho. Idatha yokusebenza kahle kanye nokuphepha evela kulolu cwaningo lwangaphambi kwe-clinical iphakamisa ibhalansi enhle yenzuzo-ingozi, esekela ukuthuthukiswa okuqhubekayo kwe-YL201 emtholampilo.
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.
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Isikhathi sokuthunyelwe: Ephreli-08-2025