Igerageza rya B7H3-target antibody-drug conjugate mu tumors zikomeye: icyiciro cya 1/1b

Ku ya 13 Werurwe 2025, ikinyamakuru mpuzamahanga gikomeye cyitwa Nature Medicine cyasohoye igerageza rya MediLink rya B7-H3 rigamije kurwanya abarwayi ba kanseri (ADC) YL201 Phase 1/1b.

Igerageza ryakozwe ryarimo igice cyo kongera urugero rw'umuti (icyiciro cya 1) n'igice cyo kongera urugero rw'umuti (icyiciro cya 1b). Abarwayi 312 bose hamwe banditswe mu bwoko butandukanye bw'ibibyimba, harimo kanseri y'ibihaha ifite uturemangingo duto (ES-SCLC), kanseri yo mu nda (NPC), kanseri y'ibihaha itari iy'uturemangingo duto, kanseri yo mu ruhu rw'umuyoboro w'amaraso n'izindi kanseri zikomeye.

Mu barwayi 287 bapimwe niba bashoboye, igipimo cy’ubutabazi bw’ibanze (ORR) cyari 40.8%, naho igipimo cyo kurwanya indwara (DCR) cyari 83.6%. Igipimo cy’ubutabazi bw’ibanze (mPFS) cyari amezi 5.9, naho igihe cy’ubutabazi bw’ibanze (mDOR) cyari amezi 6.3. Igipimo cy’ubutabazi bw’ibanze (OS) cyari kitaragera ku rugero rwo hejuru.

Mu barwayi 48 bafite indwara ya metastases yo mu bwonko, 21 nibo bapimwe; ORR yo mu mutwe yari 28.5%; naho DOR yari amezi 6.2.

Abarwayi bose bafite ES-SCLC babanje kuvurwa hakoreshejwe imiti ikomoka kuri platine, kandi 95.8% by'abarwayi nabo babanje kuvurwa hakoreshejwe antibody ya PD-1 (PD-1) cyangwa antibody ya PD-L1 (ORR). ORR yari 63.9%; DCR yari 91.7%; mPFS yari amezi 6.3; naho mDOR yari amezi 5.7. Mu bushakashatsi bwo kongera dose, abarwayi batanu bafite SCLC bahawe ubuvuzi bwa mbere bakoresheje umuti ubuza indwara wa topoisomerase 1 (topotecan cyangwa irinotecan) ni bo banditswe, umurwayi umwe gusa akaba ari we wasubije (ORR, 20%). Mu barwayi 70 bafite NPC, bose babanje kuvurwa hakoreshejwe imiti irwanya PD-L1 na platine, naho 84.3% (59/70) bafite imirongo ibiri cyangwa irenga y'ubuvuzi bwabanje. Abarwayi babiri ba NPC babonye igisubizo cyuzuye (CR), bafite ORR ya 48.6% na DCR ya 92.9%. MPFS yari amezi 7.8, naho mDOR yari amezi 8.4. Abarwayi 64 bose hamwe barwaye NSCLC yo mu bwoko bwa wild-type bapimwe, barimo 28 bafite adenocarcinoma, 12 bafite squamous cell carcinoma na 24 bafite lymphoepithelioma-like carcinoma (LELC). Muri rusange, 90.6% (58/64) by'abarwayi ba NSCLC babanje kuvurwa na PD-L1 na platinum-based chemotherapy. Agaciro ka ORR ku barwayi bafite adenocarcinoma y'ibihaha, squamous cell carcinoma na LELC kari 28.6%, 8.3% na 54.2%, uko bikurikirana, naho mDOR yari amezi 13.6, amezi 2.6 n'amezi 6.7, uko bikurikirana.

YL201 yagaragaje umutekano ukwiye kandi ifite akamaro gakomeye ku barwayi bavuwe mbere y’igihe bafite ibibyimba bikomeye, cyane cyane ku bafite kanseri imeze nk’iya ES-SCLC, NPC cyangwa kanseri imeze nk’iya lymphoepithelioma.

YL201 ni ADC nshya igizwe na antibody monoclonal anti-B7H3 iterwa n’umuti mushya wa topoisomerase 1 ukoresheje protease-cleavable linker, ifite ikigereranyo cya 8 cy’umuti-ku-antibody. YL201 yakozwe hakoreshejwe urubuga rwa MediLink rwa tumor microenvironment activable linker-payload (TMALIN), rurangwa n’umutwaro unyura cyane mu mazi, gutuza gukomeye mu mikorere y’amaraso no kurekura umutwaro ubiri urimo gucikamo ibice haba mu ruhu rw’inyuma rw’uturemangingo no mu ruhu rw’ingirabuzima fatizo muri lysosomes. Mu bushakashatsi bwakozwe mbere yo kuvura, YL201 yagaragaje imikorere ikomeye yo kurwanya tumor mu buryo butandukanye bwa CDX/PDX imbeba hamwe na SCLC, NSCLC, kanseri yo mu muhogo na kanseri y’intanga ngore. Amakuru y’ubu bushakashatsi mbere yo kuvura agaragaza ko hari inyungu n’ingaruka nziza, bishyigikira iterambere rya YL201 mu ivuriro.

Kugeza ubu, haracyari igeragezwa ryinshi ry’ikoranabuhanga rishya rirwanya kanseri mu Bushinwa rishaka abarwayi. Inama ku miti mishya n’ikoranabuhanga, ushobora kuvugana n’Ishami Mpuzamahanga ry’Ibitaro bya Oncology bya Beijing mu Karere k’Amajyepfo.

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