NMPA Yavomereza NDA ndipo Yapereka Kuwunikanso Kofunikira Kwambiri kwa Innovent's Ipilimumab Injection, Choletsa Choyamba cha CTLA-4 ku China, Kuphatikiza ndi Sintilimab ngati Chithandizo cha Neoadjuvant cha Khansa ya M'matumbo Aakulu

Pa February 22, 2025, New Drug Application (NDA) ya jakisoni wa ipilimumab (anti-CTLA-4 monoclonal antibody; R&D Code: IBI310) yavomerezedwa ndi Center for Drug Evaluation (CDE) ya China's National Medical Products Administration (NMPA) ndipo yapereka Priority Review monga chithandizo cha neoadjuvant cha khansa ya m'matumbo ya microsatellite yomwe ingachotsedwe (MSI-H) kapena mismatch repair deficiency (dMMR).

Iyi ndi njira yoyamba ya NDA ku China yogwiritsira ntchito mankhwala oletsa khansa a CTLA-4 komanso njira ina yolimbikitsira utsogoleri wa sintilimab pa chithandizo cha matenda a khansa. Chithandizo cha chitetezo chamthupi choyang'ana PD-1 ndi CTLA-4 chasintha chithandizo cha khansa, ipilimumab yokhala ndi sintilimab ngati chithandizo cha neoadjuvant ikhoza kuwonjezera kuchuluka kwa kuchotsedwa kwa R0, kukwaniritsa yankho lathunthu la matenda, ndikuchepetsa odwala ambiri ku zovuta za chemotherapy. Chithandizo chatsopanochi chikuyembekezekanso kuchepetsa kuchuluka kwa kubwereranso kwa matendawa ndikuwonjezera chiyembekezo cha nthawi yayitali, chomwe chikuyembekezeka kupindulitsa odwala khansa ya m'matumbo a MSI-H/dMMR akavomerezedwa ndi NDA.

Kuvomerezedwa kwa NDA ndi Kuwunika Kwambiri kumachokera ku zotsatira za mayeso azachipatala a Gawo 3 mwachisawawa, olamulidwa, okhala ndi malo ambiri, komanso ofunikira (NeoShot, NCT05890742) omwe adawunika chitetezo ndi mphamvu ya ipilimumab pamodzi ndi sintilimab ngati chithandizo cha neoadjuvant komanso poyerekeza ndi opaleshoni yolunjika ya khansa ya m'matumbo ya MSI-H/dMMR. Mapeto ake akuluakulu ndi kuchuluka kwa yankho lokwanira (pCR) ndi kupulumuka popanda zochitika (EFS). Kusanthula kwakanthawi ndi Independent Data Monitoring Committee (IDMC) kunawonetsa kuti mayeso a NeoShot akwaniritsa cholinga chake chachikulu.

Pofika pa 4 February, 2024, ma dotolo 101 adalembedwa (amuna: 55.4%, apakati azaka: zaka 56, ECOG PS 1: 54.5%, chiopsezo chachikulu: 76.2%) ndipo adasankhidwa mwachisawawa mu mkono A (n = 52) ndi mkono B (n = 49). Mu mkono A, dotolo 1 adasiya chithandizo msanga (kusiya). Mu mkono B, ma dotolo 4 adasiya chithandizo msanga (kusiya 1, 1 adamwalira, 2 adapitiliza ndi neoadjuvant sintilimab). Kuchotsa opaleshoni kokonzedwa kunachitika m'magawo 51 (98.1%) mu mkono A ndi magawo 45 (91.8%) mu mkono B. Kuwunika pambuyo pa opaleshoni kunawonetsa kuti palibe mgwirizano wokonza bwino (pMMR) mu 1 pt iliyonse mu mkono A ndi mkono B. Chiwerengero cha pCR chinali 80.0% (40/50, 95%CI: 66.3-90.0) mu mkono A poyerekeza ndi 47.7% (21/44, 95%CI: 32.5-63.3) mu mkono B (p = 0.0007). Magawo onse omwe adachitidwa opaleshoni anali ndi R0 resection. Nthawi yapakati pakati pa mlingo woyamba wa chithandizo cha neoadjuvant ndi opaleshoni inali masiku 47 (kuyambira: 35-82). Kuchedwa kwa opaleshoni kunachitika m'magawo atatu kuphatikiza mapointi awiri mu mkono A chifukwa cha giredi 2 hypothyroidism (kuchedwa kwa masiku awiri) ndi giredi 1 hyperthyroidism (kuchedwa kwa masiku 13), ndi giredi 1 mu mkono B pazifukwa zina (kuchedwa kwa masiku 26). Zochitika zoyipa zomwe zimachitika mwadzidzidzi (TEAEs) zinachitika m'magawo 46 (88.5%, giredi ≥3 mu mapointi 13) mu mkono A ndi mapointi 39 (79.6%, giredi ≥3 mu mapointi 9) mu mkono B. Zochitika zoyipa zokhudzana ndi chitetezo chamthupi (irAEs) zinachitika m'magawo 22 (42.3%) mu mkono A ndi mapointi 18 (36.7%) mu mkono B. Giredi ≥3 irAEs zinachitika m'magawo atatu mu mkono A, kuphatikizapo myocarditis yoyambitsidwa ndi chitetezo chamthupi, ileus ndi enteritis, ndi mapointi 4 mu mkono B, kuphatikizapo alanine aminotransferase increased, rash, hypothyroidism ndi myocarditis. Matenda oopsa a TRAE adachitika m'magawo 4 (7.7%) mu mkono A ndi magawo 3 (6.1%) mu mkono B. TRAE yomwe idapangitsa kuti munthu afe idachitika m'magawo 1 mu mkono B (myocarditis).

About Ipilimumab

Ipilimumab (R&D code: IBI310) ndi jakisoni wa antibody wa munthu wopangidwa payekha ndi Innovent. Ipilimumab imatha kumangirira antigen 4 (CTLA-4) ya cytotoxic lymphocyte, motero imaletsa kuletsa kwa maselo a T omwe amathandizidwa ndi CTLA-4, kulimbikitsa kuyambitsa ndi kufalikira kwa maselo a T, kukonza chitetezo cha mthupi cha chotupa, komanso kukwaniritsa zotsatira zotsutsana ndi chotupa.

NDA ya ipilimumab pamodzi ndi sintilimab ngati chithandizo cha neoadjuvant cha khansa ya m'matumbo ya microsatellite yomwe ingachotsedwe (MSI-H) kapena mismatch repair deficit (dMMR) ili pansi pa kuwunika kwa NMPA ndipo yapatsidwa Priority Review.

About Sintilimab

Sintilimab, yomwe imagulitsidwa ngati TYVYT (jakisoni wa sintilimab) ku China, ndi antibody ya PD-1 immunoglobulin G4 monoclonal yomwe idapangidwa ndi Innovent ndi Eli Lilly and Company. Sintilimab ndi mtundu wa antibody ya immunoglobulin G4 monoclonal, yomwe imamangirira ku mamolekyu a PD-1 pamwamba pa maselo a T, imatseka njira ya PD-1 / PD-Ligand 1 (PD-L1), ndikuyambitsanso maselo a T kuti aphe maselo a khansa.

Pakadali pano, pali mayesero ambiri azachipatala a ukadaulo watsopano wothana ndi khansa ku China omwe akufuna odwala. Mukafunsira mankhwala ndi ukadaulo watsopano, mutha kulumikizana ndi Dipatimenti Yapadziko Lonse ya Chipatala cha Oncology ku Beijing South Region.

Nambala ya Foni: 4008803716

Email：myimmnet@163.com

Zolemba

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

2.Chithandizo cha neoadjuvant cha IBI310 (anti-CTLA-4 antibody) kuphatikiza sintilimab (anti-PD-1 antibody) mwa odwala omwe ali ndi microsatellite instability-high/mismatch repair-deficient colorectal cancer: Zotsatira kuchokera ku kafukufuku wa Ib wosankhidwa mwachisawawa, wotseguka, | Journal of Clinical Oncology (ascopubs.org)

3.信达生物 (innoventbio.com)