I-NMPA Yamukela I-NDA Futhi Inikeza Isibonelelo Sokubuyekezwa Okubalulekile Kokuqokwa Komjovo We-Ipilimumab we-Innovent, Umjovo Wokuqala Wasekhaya we-CTLA-4 eShayina, ohlanganiswe ne-Sintilimab njengokwelashwa kwe-Neoadjuvant komdlavuza wamathumbu amakhulu.

Ngomhlaka-22 kuNhlolanja 2025, i-New Drug Application (NDA) yomjovo we-ipilimumab (anti-CTLA-4 monoclonal antibody; Ikhodi ye-R&D: IBI310) yamukelwe yi-Center for Drug Evaluation (CDE) ye-China's National Medical Products Administration (NMPA) futhi yanikeza i-Priority Review igama elihlanganiswe ne-sintilimab njengokwelashwa kwe-neoadjuvant kwe-microsatellite instability-high (MSI-H) noma i-mismatch repair deficiency (dMMR) colon cancer.

Lena yi-NDA yokuqala yaseShayina yomuthi wokuvimbela i-CTLA-4 wasekhaya kanye nesinye isigameko esiqinisa isikhundla sobuholi se-sintilimab ekwelashweni ngomdlavuza. Ukwelashwa kokuvimbela izivikelo zomzimba (i-ICB) okuqondiswe ku-PD-1 kanye ne-CTLA-4 kushintshe ukwelashwa komdlavuza, i-ipilimumab ene-sintilimab njengokwelashwa kwe-neoadjuvant ingakhuphula izinga lokususwa kwe-R0, ifinyelele impendulo ephelele ye-pathological, futhi ikhulule iningi leziguli emithwalweni ye-chemotherapy ye-adjuvant. Lokhu kwelashwa okusha kulindeleke ukuthi kunciphise izinga lokubuyela emuva futhi kuthuthukise ukubikezela kwesikhathi eside, okulindeleke ukuthi kuzuze iziguli ezinomdlavuza wamathumbu amakhulu i-MSI-H/dMMR lapho kuvunyelwa i-NDA.

Ukwamukelwa kwe-NDA kanye nokuqokwa kwe-Priority Review kusekelwe emiphumeleni evela esivivinyweni somtholampilo seSigaba sesi-3 esingahleliwe, esilawulwayo, esinama-centre amaningi, esibalulekile (NeoShot, NCT05890742) esihlole ukuphepha kanye nokusebenza kahle kwe-ipilimumab kuhlanganiswe ne-sintilimab njengokwelashwa kwe-neoadjuvant futhi uma kuqhathaniswa nokuhlinzwa okuqondile kwe-MSI-H/dMMR colon cancer. Iziphetho eziyinhloko izinga le-pathologic complete response (pCR) kanye nokusinda okungenazigameko (EFS). Ukuhlaziywa kwesikhashana yi-Independent Data Monitoring Committee (IDMC) kubonise ukuthi isivivinyo se-NeoShot sifinyelele esiphethweni saso esiyinhloko.

Kusukela ngomhlaka-4 kuNhlolanja 2024, kwabhaliswa ama-pts ayi-101 (abesilisa: 55.4%, ubudala obuphakathi: iminyaka engama-56, i-ECOG PS 1: 54.5%, ingozi ephezulu: 76.2%) futhi kwafakwa ngokungahleliwe engalweni A (n = 52) kanye nengalo B (n = 49). Engalweni A, i-pt eli-1 laqedwa ukwelashwa kusenesikhathi (ukuhoxiswa). Engalweni B, ama-pts ama-4 aqedwa ukwelashwa kusenesikhathi (ukuhoxiswa okukodwa, oyedwa washona, ama-2 aqhubeka ne-neoadjuvant sintilimab). Ukuhlinzwa kokuhlinzwa okuhleliwe kwenziwe kuma-pts angu-51 (98.1%) engalweni A kanye nama-pts angu-45 (91.8%) engalweni B. Ukuhlolwa ngemva kokuhlinzwa kwembule ukuthi i-repair-proficient yokulungisa ayifani (pMMR) ku-1 pt ngayinye engalweni A kanye nengalo B. Amanani e-pCR ayengu-80.0% (40/50, 95%CI: 66.3-90.0) engalweni A vs 47.7% (21/44, 95%CI: 32.5-63.3) engalweni B (p = 0.0007). Wonke ama-pts ahlinzwe ayenokuhlinzwa kwe-R0. Isikhathi esimaphakathi phakathi komthamo wokuqala wokwelashwa kwe-neoadjuvant kanye nokuhlinzwa kwakuyizinsuku ezingu-47 (ibanga: 35-82). Ukulibaziseka kokuhlinzwa kwenzeke kuma-pts amathathu kufaka phakathi ama-pts amabili engalweni A ngenxa ye-hypothyroidism yebanga lesi-2 (ukubambezeleka kwezinsuku ezi-2) kanye ne-hyperthyroidism yebanga loku-1 (ukubambezeleka kwezinsuku eziyi-13), kanye ne-pt eli-1 engalweni B ngesinye isizathu (ukubambezeleka kwezinsuku ezingama-26). Imicimbi emibi ephuthumayo yokwelashwa (ama-TEAE) yenzeke kuma-pts angu-46 (88.5%, ibanga≥3 kuma-pts ayi-13) engalweni A kanye nama-pts angu-39 (79.6%, ibanga≥3 kuma-pts ayi-9) engalweni B. Imicimbi emibi ehlobene nokuzivikela komzimba (ama-irAE) yenzeke kuma-pts angu-22 (42.3%) engalweni A kanye nama-pts ayi-18 (36.7%) engalweni B. Ama-irAE ebanga ≥3 enzeke kuma-pts amathathu engalweni A, kufaka phakathi i-myocarditis ebangelwa amasosha omzimba, i-ileus kanye ne-enteritis, kanye nama-pts angu-4 engalweni B, kufaka phakathi ukwanda kwe-alanine aminotransferase, ukuqubuka, i-hypothyroidism kanye ne-myocarditis. I-TRAEs enkulu yenzeke kuma-pts angu-4 (7.7%) engalweni A kanye nama-pts angu-3 (6.1%) engalweni B. I-TRAE eyaholela ekufeni yenzeke kuma-pts angu-1 engalweni B (myocarditis).

Mayelana ne-Ipilimumab

I-Ipilimumab (ikhodi ye-R&D: IBI310) iwumjovo we-antibody we-monoclonal womuntu ophelele owakhiwe ngokuzimela yi-Innovent. I-Ipilimumab ingabopha ngqo i-antigen 4 (CTLA-4) ehlobene ne-cytotoxic T lymphocyte, ngaleyo ndlela ivimbele ukuvinjelwa kwe-T cell okubangelwa yi-CTLA-4, ikhuthaze ukusebenza kwe-T cell kanye nokwanda kwayo, ithuthukise impendulo yomzimba yesimila, futhi ifinyelele imiphumela yokulwa nesimila.

I-NDA ye-ipilimumab ngokuhlanganiswa ne-sintilimab njengokwelashwa kwe-neoadjuvant kwe-microsatellite instability-high (MSI-H) noma i-mismatch repair deficient (dMMR) colon cancer ingaphansi kokubuyekezwa kwe-NMPA futhi inikezwe igama elithi Priority Review.

Mayelana ne-Sintilimab

I-Sintilimab, ethengiswa njenge-TYVYT (umjovo we-sintilimab) eShayina, iyi-antibody ye-PD-1 immunoglobulin G4 monoclonal eyakhiwe ngokubambisana yi-Innovent no-Eli Lilly and Company. I-Sintilimab uhlobo lwe-antibody ye-immunoglobulin G4 monoclonal, ebopha kuma-molecule e-PD-1 ebusweni bama-T-cell, ivimbe indlela ye-PD-1 / PD-Ligand 1 (PD-L1), futhi ivuselele ama-T-cell ukubulala amaseli omdlavuza.

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.

Inombolo yocingo: 4008803716

Email：myimmnet@163.com

Izinkomba

1.https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d

2.Ukwelashwa kwe-Neoadjuvant kwe-IBI310 (i-anti-CTLA-4 antibody) kanye ne-sintilimab (i-anti-PD-1 antibody) ezigulini ezine-microsatellite instability-high/mismatch repair-deficient colorectal cancer: Imiphumela evela ocwaningweni lwe-Ib lwesigaba esingahleliwe, olunelebula evulekile. | Ijenali ye-Clinical Oncology (ascopubs.org)

3.信达生物 (innoventbio.com)