NMPA Yagamuchira NDA uye Yapa Rubatsiro Rwekutanga Kuongororwa Kusarudzwa kweInnovent's Ipilimumab Injection, Mushonga Wekutanga weCTLA-4 weMusha muChina, pamwe chete neSintilimab seNeoadjuvant Mushonga weKenza yeMatumbu Makuru

Musi wa22 Kukadzi 2025, New Drug Application (NDA) yekubaiwa ipirimumab (anti-CTLA-4 monoclonal antibody; R&D Code: IBI310) yakagamuchirwa neCenter for Drug Evaluation (CDE) yeChina's National Medical Products Administration (NMPA) uye yakapihwa Priority Review zita pamwe chete ne sintilimab senzira yekurapa cancer yekoloni inobviswa inonzi microsatellite instability-high (MSI-H) kana mismatch repair deficient (dMMR).

Iyi ndiyo NDA yekutanga muChina yemushonga weCTLA-4 inhibitor wemuno uye chimwe chiitiko chikuru chinosimbisa chinzvimbo chehutungamiriri hwesintilimab mukurapa kenza. Kurapa kwekudzivirira immune checkpoint (ICB) kwakanangana nePD-1 neCTLA-4 kwakachinja kurapwa kwekenza, ipilimumab ne sintilimab semushonga we neoadjuvant kunogona kuwedzera chiyero chekubvisa R0, kuwana mhinduro yakakwana yezvirwere, uye kurerutsira ruzhinji rwevarwere kubva mumitoro ye adjuvant chemotherapy. Kurapa uku kutsva kunotarisirwawo kuderedza chiyero chekudzoka kwechirwere uye kuvandudza fungidziro yenguva refu, inotarisirwa kubatsira varwere veMSI-H/dMMR vane kenza yekoloni kana NDA yabvumidza.

Kugamuchirwa kweNDA uye kusarudzwa kwePriority Review kwakavakirwa pamhedzisiro yekuyedzwa kwekiriniki kwechikamu chechitatu chePhase randomized, controlled, multicenter, pical privative (NeoShot, NCT05890742) iyo yakaongorora kuchengetedzeka uye kushanda kweipilimumab pamwe chete ne sintilimab se neoadjuvant therapy uye zvichienzaniswa nekuvhiyiwa kwakananga kweMSI-H/dMMR colon cancer. Magumo makuru i pathologic complete response (pCR) rate uye event-free survival (EFS). Ongororo yechinguvana neIndependent Data Monitoring Committee (IDMC) yakaratidza kuti NeoShot trial yasvika padanho rayo rekutanga.

Kubva musi wa4 Kukadzi 2024, vanhu 101 vakanyoreswa (varume: 55.4%, zera repakati: makore 56, ECOG PS 1: 54.5%, njodzi huru: 76.2%) uye vakaiswa muchikamu A (n = 52) uye muchikamu B (n = 49). Muchikamu A, munhu mumwe chete akamiswa kurapwa nekukurumidza (kurega). Muchikamu B, vanhu vana vakamiswa kurapwa nekukurumidza (munhu mumwe chete akarega, mumwe akafa, vaviri vakaramba vachitora mishonga yekurapa yeNeoadjuvant Sintilimab). Kuvhiyiwa kwakarongwa kwakaitwa mumapfundo makumi mashanu nerimwe (98.1%) muruoko A uye makumi mana nemashanu (91.8%) muruoko B. Ongororo yemushure mekuvhiyiwa yakaratidza kusawirirana kwekugadzirisa (pMMR) mupfundo rimwe chete muruoko A neruoko B. Mwero wepCR waiva 80.0% (40/50, 95%CI: 66.3-90.0) muruoko A vs 47.7% (21/44, 95%CI: 32.5-63.3) muruoko B (p = 0.0007). Mapfundo ese akaitwa oparesheni aive neR0 resection. Nguva yepakati pakati pedosi yekutanga yekurapwa neoadjuvant nekuvhiyiwa yaive mazuva makumi mana nemanomwe (nguva: 35-82). Kunonoka kwekuvhiyiwa kwakaitika mumapoinzi matatu kusanganisira mapoinzi maviri muruoko A nekuda kwe grade 2 hypothyroidism (kunonoka kwemazuva maviri) uye grade 1 hyperthyroidism (kunonoka kwemazuva gumi nematatu), uye 1 pt muruoko B nekuda kwechimwe chikonzero (kunonoka kwemazuva makumi maviri nematanhatu). Zviitiko zvakaipa zvinouya nekukurumidza (TEAEs) zvakaitika mumapoinzi makumi mana nematanhatu (88.5%, grade≥3 mumapoinzi gumi nematatu) muruoko A uye 39 (79.6%, grade≥3 mumapoinzi mapfumbamwe) muruoko B. Zviitiko zvakaipa zvine chekuita neimmune (irAEs) zvakaitika mumapoinzi makumi maviri nemaviri (42.3%) muruoko A uye 18 (36.7%) muruoko B. Giredhi ≥3 irAEs dzakaitika mumapoinzi matatu muruoko A, kusanganisira immune-mediated myocarditis, ileus uye enteritis, uye mumapoinzi mana muruoko B, kusanganisira alanine aminotransferase increased, rash, hypothyroidism uye myocarditis. Matambudziko makuru eTRAE akaitika muzvikamu zvina (7.7%) paruoko A uye zvikamu zvitatu (6.1%) paruoko B. TRAE yakakonzera rufu yakaitika muzvikamu zvina (1 pt) paruoko B (myocarditis).

Nezve Ipilimumab

Ipilimumab (kodhi yeR&D: IBI310) ijekiseni remaantibody emunhu akagadzirwa ega neInnovent. Ipilimumab inogona kusunga cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) neCTLA-4, nokudaro ichivhara kudzivirira kweT cell kwakakonzerwa neCTLA-4, ichikurudzira kushanda kweT cell uye kuwanda kwayo, ichivandudza mhinduro yekudzivirira gomarara, uye ichibudirira pakurwisa gomarara.

NDA yeipilimumab pamwe chete ne sintilimab senzira yekurapa cancer yekoloni ine utachiona hwe microsatellite husina kugadzikana (MSI-H) kana mismatch repair deficient (dMMR) iri pasi peongororo yeNMPA uye yakapihwa Priority Review.

NezveSintilimab

Sintilimab, inotengeswa seTYVYT (sintilimab injection) muChina, iPD-1 immunoglobulin G4 monoclonal antibody yakagadzirwa pamwe chete naInnovent naEli Lilly and Company. Sintilimab imhando yeimmunoglobulin G4 monoclonal antibody, iyo inosunga kumamorekuru ePD-1 pamusoro pemasero eT, inovhara nzira yePD-1 / PD-Ligand 1 (PD-L1), uye inomutsazve masero eT kuti auraye masero egomarara.

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.

Nhamba yefoni: 4008803716

Email：myimmnet@163.com

Mareferensi

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

2.Kurapa kweIBI310 (anti-CTLA-4 antibody) pamwe ne sintilimab (anti-PD-1 antibody) muvarwere vane microsatellite instability-high/mismatch repair-deficient colorectal cancer: Mhedzisiro kubva mukudzidza kweIb kwakaitwa ne randomized, open-labeled. | Journal of Clinical Oncology (ascopubs.org)

3.信达生物 (innoventbio.com)