Musi wa13 Kurume 2025, magazini yepamusoro yepasi rose yeNature Medicine yakaburitsa bvunzo yeMediLink yeB7-H3 ichitarisa antibody drug conjugate (ADC) YL201 Phase 1/1b.
Kuedzwa kwacho kwaisanganisira chikamu chekukwira kwedosi (chikamu chekutanga) uye chikamu chekuwedzerwa kwedosi (chikamu chekutanga b). Varwere vanosvika 312 vakanyoreswa mumhando dzakasiyana dzemabundu, kusanganisira kenza yemapapu yemasero madiki (ES-SCLC), nasopharyngeal carcinoma (NPC), kenza yemapapu yemasero madiki, esophageal squamous cell carcinoma nedzimwe bundu dzakasimba.
Pakati pevarwere 287 vakaongororwa kuti vanobudirira sei, chiyero chekupindura chakanangana (ORR) chaive 40.8%, uye chiyero chekudzora chirwere (DCR) chaive 83.6%. Kurarama kwepakati pasina kufambira mberi (mPFS) kwaive kwemwedzi 5.9, uye nguva yepakati yekupindura (mDOR) yaive mwedzi 6.3. Kurarama kwepakati (OS) kwaive kusati kwakura.
Pakati pevarwere makumi mana nevasere vane chirwere chepfungwa chakapararira muuropi, makumi maviri nemumwe ndivo vakaongororwa; ORR yemukati memusoro yaive 28.5%; uye DOR yaive mwedzi mitanhatu nehafu.
Varwere vese vane ES-SCLC vakamborapwa ne platinum-based chemotherapy, uye 95.8% yevarwere vakamborapwa ne programmed death 1 (PD-1) kana programmed death ligand 1 (PD-L1) antibody. ORR yaive 63.9%; DCR yaive 91.7%; mPFS yaive 6.3 mwedzi; uye mDOR yaive 5.7 mwedzi. Muchidzidzo chekuwedzera kwedosi, varwere vashanu vane SCLC vakagamuchira kurapwa kwekutanga ne topoisomerase 1 inhibitor (topotecan kana irinotecan) vakanyoreswa, murwere mumwe chete ndiye akapindura (ORR, 20%). Pavarwere makumi manomwe vane NPC, vese vakamborapwa ne anti-PD-L1 ne platinum-based chemotherapy, uye 84.3% (59/70) vaive nemitsara miviri kana kupfuura yekurapa kwakamboitwa kare. Vaviri vevarwere vaiva neNPC vakawana mhinduro yakakwana (CR), vaine ORR ye48.6% uye DCR ye92.9%. MPFS yaive mwedzi 7.8, uye mDOR yaive mwedzi 8.4. Huwandu hwevarwere makumi matanhatu nevana vane wild-type NSCLC vakaongororwa, kusanganisira 28 vane adenocarcinoma, 12 vane squamous cell carcinoma uye 24 vane lymphoepithelioma-like carcinoma (LELC). Huwandu hwevarwere vaiva neNSCLC hwakamborapwa ne anti-PD-L1 uye platinum-based chemotherapy. Huwandu hweORR hwevarwere vaiva ne lung adenocarcinoma, squamous cell carcinoma neLELC hwaive 28.6%, 8.3% uye 54.2%, zvichiteerana, uye mDOR yaive mwedzi 13.6, mwedzi 2.6 nemwedzi 6.7, zvichiteerana.
YL201 yakaratidza kuchengetedzeka kunogamuchirika uye kushanda zvakanaka muvarwere vakamborapwa zvakanyanya vane bundu rakasimba, kunyanya kune avo vane ES-SCLC, NPC kana lymphoepithelioma-like carcinoma.
YL201 iADC itsva ine human anti-B7H3 monoclonal antibody yakabatana nechinhu chitsva chetopoisomerase 1 inhibitor kuburikidza neprotease-cleavable linker, ine huwandu hwemishonga-ku-antibody hwe8. YL201 yakagadzirwa ichishandisa MediLink's tumor microenvironment activable linker-payload (TMALIN) platform, iyo inoratidzwa ne linker-payload inonyungudika zvikuru, kugadzikana kunoshamisa mukutenderera kweropa uye nzira mbiri yekuburitsa payload inosanganisira kutsemuka kwekunze kwemuviri mu tumor microenvironment uye mukati memasero mukati me lysosomes. Mukudzidza kwepamberi pekiriniki, YL201 yakaratidza simba rekudzivirira tumor mumhando dzakasiyana dzeCDX/PDX mouses dzine SCLC, NSCLC, urophageal cancer uye ovarian cancer. Ruzivo rwekushanda nekuchengetedzwa kubva mukudzidza kwepamberi pekiriniki urwu runoratidza kuti kune kuenzana kwakanaka pakati pengozi nerubatsiro, zvichitsigira kukura kweYL201 mukiriniki.
Parizvino, kuchine miedzo yakawanda yekiriniki yehunyanzvi hutsva hwekurwisa gomarara muChina huri kutsvaga varwere. Kana muchida kubvunzana nezvemishonga mitsva netekinoroji, munogona kubata Dhipatimendi reBeijing South Region Oncology Hospital International.
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Nguva yekutumira: Kubvumbi-08-2025