I-NMPA Yamkela i-NDA kwaye Izibonelelo Ziyayibeka I-Ipilimumab Injection ye-Innovent, i-CTLA-4 Inhibitor yokuqala yasekhaya eTshayina, idityaniswe ne-Sintilimab njengoNyango lwe-Neoadjuvant loMhlaza weColon

Ngomhla wama-22 kuFebruwari 2025, iSicelo seDrug esitsha (NDA) sokufakwa kwe-ipilimumab (i-anti-CTLA-4 monoclonal antibody; iKhowudi ye-R&D: IBI310) samkelwe yiZiko loVavanyo lweDrug (CDE) le-China's National Medical Products Administration (NMPA) kwaye sanikwa igama elithi Priority Review kunye ne-sintilimab njengonyango lwe-neoadjuvant kwi-microsatellite instability-high (MSI-H) okanye i-mismatch repair deficient (dMMR) colon cancer.

Le yi-NDA yokuqala yaseTshayina ye-CTLA-4 inhibitor yasekhaya kunye nenye inqaku elibalulekileyo eliqinisa isikhundla sobunkokeli se-sintilimab kwi-immunotherapy yomhlaza. Unyango lwe-immune checkpoint blockade (ICB) olujolise kwi-PD-1 kunye ne-CTLA-4 lutshintshe unyango lwe-oncology, i-ipilimumab ene-sintilimab njengonyango lwe-neoadjuvant inokunyusa izinga lokususwa kwe-R0, ifumane impendulo epheleleyo ye-pathological, kwaye ikhulule uninzi lwezigulane kwimithwalo ye-chemotherapy encedisayo. Olu nyango lutsha kulindeleke ukuba lunciphise izinga lokubuyela kwakhona kwaye luphucule ukubikezela kwexesha elide, okulindeleke ukuba luncede izigulane ezinomhlaza wamathumbu amakhulu ze-MSI-H/dMMR xa zivunyiwe yi-NDA.

Ukwamkelwa kwe-NDA kunye nokubekwa kwePriority Review kusekelwe kwiziphumo ezivela kuvavanyo lweklinikhi lweSigaba sesi-3 olucwangcisiweyo, olulawulwayo, oluneendawo ezininzi, olubalulekileyo (NeoShot, NCT05890742) oluvavanye ukhuseleko kunye nokusebenza kakuhle kwe-ipilimumab edityaniswe ne-sintilimab njengonyango lwe-neoadjuvant kwaye xa kuthelekiswa notyando oluchanekileyo lomhlaza wamathumbu amakhulu we-MSI-H/dMMR. Iziphumo eziphambili zizinga lempendulo epheleleyo ye-pathologic (pCR) kunye nokusinda okungenaziganeko (EFS). Uhlalutyo lwexeshana yiKomiti eLawulayo yoLawulo lweDatha eZimeleyo (IDMC) lubonise ukuba uvavanyo lweNeoShot lufikelele kwinqanaba lalo eliphambili.

Ukususela nge-4 kaFebruwari 2024, kwabhaliswa amagosa ali-101 (amadoda: 55.4%, ubudala obuphakathi: 56 iminyaka, i-ECOG PS 1: 54.5%, umngcipheko ophezulu: 76.2%) kwaye afakwa ngokungacwangciswanga kwingalo A (n = 52) nakwingalo B (n = 49). Kwingalo A, i-1 pt yayiyekile unyango kwangoko (ukurhoxiswa). Kwingalo B, amagosa ama-4 ayekile unyango kwangoko (ukurhoxiswa e-1, e-1 yafa, amagosa ama-2 aqhubeka ne-neoadjuvant sintilimab). Utyando olucwangcisiweyo lwenziwe kwii-51 (98.1%) pts engalweni A kunye nee-45 (91.8%) pts engalweni B. Uvavanyo lwasemva kotyando lubonakalise ukuba akukho buchule bokulungisa obufanelekileyo (pMMR) kwi-1 pt nganye engalweni A nakwingalo B. Amanqanaba e-pCR ayeyi-80.0% (40/50, 95%CI: 66.3-90.0) engalweni A ngokuchasene ne-47.7% (21/44, 95%CI: 32.5-63.3) engalweni B (p = 0.0007). Zonke ii-pts ezifumene utyando zazinotyando lwe-R0 resection. Ixesha eliphakathi phakathi kwedosi yokuqala yonyango lwe-neoadjuvant kunye notyando yayiziintsuku ezingama-47 (uluhlu: 35-82). Ukulibaziseka kotyando kwenzeke kwi-3 pts kuquka i-2 pts engalweni A ngenxa ye-grade 2 hypothyroidism (ukulibaziseka kweentsuku ezi-2) kunye ne-grade 1 hyperthyroidism (ukulibaziseka kweentsuku ezili-13), kunye ne-1 pt engalweni B ngesinye isizathu (ukulibaziseka kweentsuku ezingama-26). Iziganeko ezimbi ezivelelayo zonyango (ii-TEAE) zenzeke kwi-46 pts (88.5%, i-grade≥3 kwi-13 pts) engalweni A kunye ne-39 pts (79.6%, i-grade≥3 kwi-9 pts) engalweni B. Iziganeko ezimbi ezinxulumene nomzimba (ii-irAE) zenzeke kwi-22 pts (42.3%) engalweni A kunye ne-18 pts (36.7%) engalweni B. I-grade ≥3 irAEs zenzeke kwi-3 pts engalweni A, kuquka i-immune-mediated myocarditis, ileus kunye ne-enteritis, kunye ne-4 pts engalweni B, kuquka i-alanine aminotransferase increased, rash, hypothyroidism kunye ne-myocarditis. I-TRAEs enzulu yenzeke kwi-4 (7.7%) pts engalweni A kunye ne-3 (6.1%) pts engalweni B. I-TRAE ekhokelela ekufeni yenzeke kwi-1 pt engalweni B (myocarditis).

Malunga ne-Ipilimumab

I-Ipilimumab (ikhowudi ye-R&D: IBI310) yinaliti ye-antibody ye-monoclonal epheleleyo yomntu eyenziwe ngokuzimeleyo yi-Innovent. I-Ipilimumab inokubopha ngokukodwa i-antigen 4 enxulumene ne-cytotoxic T lymphocyte-associated antigen (CTLA-4), ngaloo ndlela ithintele ukuthintelwa kwe-CTLA-4 phakathi kwe-T cell, ikhuthaza ukusebenza kunye nokwanda kwe-T cell, iphucula impendulo yomzimba yokuzikhusela kwi-tumor, kwaye ifezekise iziphumo zokulwa ne-tumor.

I-NDA ye-ipilimumab kunye ne-sintilimab njengonyango lwe-neoadjuvant lwe-microsatellite instability-high (MSI-H) okanye umhlaza wamathumbu ongakwaziyo ukulungiswa (dMMR) iphantsi kophononongo lwe-NMPA kwaye inikwe i-Priority Review.

Malunga neSintilimab

I-Sintilimab, ethengiswa njenge-TYVYT (isitofu se-sintilimab) eTshayina, yi-PD-1 immunoglobulin G4 monoclonal antibody eyenziwe yi-Innovent kunye ne-Eli Lilly and Company. I-Sintilimab luhlobo lwe-immunoglobulin G4 monoclonal antibody, ebopha kwiimolekyuli ze-PD-1 kumphezulu wee-T-cells, ivale indlela ye-PD-1 / PD-Ligand 1 (PD-L1), kwaye ivuselele ii-T-cells ukubulala iiseli zomhlaza.

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.

Inombolo yefowuni: 4008803716

Email：myimmnet@163.com

Iireferensi

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

2.Unyango lwe-Neoadjuvant lwe-IBI310 (i-anti-CTLA-4 antibody) kunye ne-sintilimab (i-anti-PD-1 antibody) kwizigulane ezine-microsatellite instability-high/mismatch repair-deficient colorectal cancer: Iziphumo ezivela kuphando lwe-Ib olucwangcisiweyo, oluvulekileyo, oluneelebheli. | Ijenali ye-Clinical Oncology (ascopubs.org)

3.信达生物 (innoventbio.com)