I te 22 o Pēpuere, 2025, kua whakaaetia te New Drug Application (NDA) mō te werohanga ipilimumab (anti-CTLA-4 monoclonal antibody; R&D Code: IBI310) e te Center for Drug Evaluation (CDE) o te National Medical Products Administration (NMPA) o Haina, ā, kua whakawhiwhia ki te Priority Review hei maimoatanga neoadjuvant mō te mate pukupuku koroni e kore e taea te tango i te microsatellite instability-high (MSI-H) me te mismatch repair deficient (dMMR).
Koinei te NDA tuatahi a Haina mō te aukati CTLA-4 ā-rohe, ā, ko tētahi atu tohu nui e whakapakari ana i te tūranga kaiārahi o te sintilimab i roto i te rongoā ārai mate pukupuku. Kua hurihia e te rongoā aukati ārai mate (ICB) e aro ana ki te PD-1 me te CTLA-4 te maimoatanga oncology, ka taea e te ipilimumab me te sintilimab hei maimoatanga neoadjuvant te whakanui ake i te tere tango R0, te whakatutuki i te urupare mate katoa, me te whakaora i te nuinga o ngā tūroro mai i ngā taumahatanga chemotherapy adjuvant. E matapaetia ana hoki ka whakaitihia e tēnei maimoatanga hou te tere hokinga mai me te whakapai ake i te matapae mo te wā roa, e matapaetia ana ka whai hua ki ngā tūroro mate pukupuku koroni MSI-H/dMMR ina whakaaetia e te NDA.
Ko te whakaaetanga NDA me te tohu Arotake Matua i ahu mai i ngā hua mai i tētahi whakamātautau haumanu Wāhanga 3 matapōkere, whakahaeretia, maha-pokapū, matua (NeoShot, NCT05890742) i arotake i te haumaru me te whai huatanga o te ipilimumab i honoa ki te sintilimab hei rongoā neoadjuvant, me te whakataurite ki te pokanga radical tika mō te mate pukupuku koroni MSI-H/dMMR. Ko ngā pito whakamutunga matua ko te reiti urupare katoa pathologic (pCR) me te oranga kore-takahanga (EFS). I whakaatuhia e te tātaritanga wā poto a te Komiti Aroturuki Raraunga Motuhake (IDMC) kua tutuki i te whakamātautau NeoShot tōna pito whakamutunga matua.
I te 4 o Pēpuere, 2024, 101 ngā tohu i whakaurua (tāne: 55.4%, tau toharite: 56 tau, ECOG PS 1: 54.5%, mōrearea nui: 76.2%) ā, i whakarōpūtia matapōkeretia ki te ringa A (n = 52) me te ringa B (n = 49). I te ringa A, 1 te tohu i mutu wawe te maimoatanga (whakamutu). I te ringa B, 4 ngā tohu i mutu wawe te maimoatanga (1 i mutu, 1 i mate, 2 i haere tonu te neoadjuvant sintilimab). I mahia te tangohanga whakaora kua whakaritea mō te 51 (98.1%) ngā tohu i te ringa A me te 45 (91.8%) ngā tohu i te ringa B. I whakaatuhia e te aromatawai i muri i te pokanga he koretake te whakatikatika (pMMR) i te 1 tohu i ia ringa A me te ringa B. Ko ngā reiti pCR he 80.0% (40/50, 95%CI: 66.3-90.0) i te ringa A, ki te 47.7% (21/44, 95%CI: 32.5-63.3) i te ringa B (p = 0.0007). Ko ngā tohu katoa i whiwhi pokanga he tangohanga R0. Ko te wā waenga i waenga i te horopeta tuatahi o te maimoatanga neoadjuvant me te pokanga he 47 ngā rā (awhe: 35-82). I puta te whakaroa o te pokanga i roto i te 3 ngā tohu tae atu ki te 2 ngā tohu i te ringa A nā te hypothyroidism taumata 2 (2 ngā rā whakaroa) me te hyperthyroidism taumata 1 (13 ngā rā whakaroa), me te 1 tohu i te ringa B mō tētahi atu take (26 ngā rā whakaroa). I puta ngā pānga kino ohorere-maimoatanga (TEAE) i roto i te 46 ngā tohu (88.5%, taumata ≥3 i roto i te 13 ngā tohu) i te ringa A me te 39 ngā tohu (79.6%, taumata ≥3 i roto i te 9 ngā tohu) i te ringa B. I puta ngā pānga kino e pā ana ki te ārai mate (irAE) i roto i te 22 ngā tohu (42.3%) i te ringa A me te 18 ngā tohu (36.7%) i te ringa B. I puta ngā irAE taumata ≥3 i roto i te 3 ngā tohu i te ringa A, tae atu ki te myocarditis nā te ārai mate, te ileus me te enteritis, ā, i roto i te 4 ngā tohu i te ringa B, tae atu ki te pikinga o te alanine aminotransferase, te ponana, te hypothyroidism me te myocarditis. I puta ngā TRAE kino i roto i te 4 (7.7%) ngā tohu i te ringa A me te 3 (6.1%) ngā tohu i te ringa B. I puta te TRAE i mate ai te 1 tohu i te ringa B (myocarditis).
Mō Ipilimumab
Ko te Ipilimumab (waehere R&D: IBI310) he werohanga paturopi monoclonal tangata katoa i whakawhanakehia motuhaketia e Innovent. Ka taea e te Ipilimumab te here motuhake i te cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), ā, ka ārai i te aukati pūtau T e whakahaerehia ana e CTLA-4, ka whakatairanga i te whakahohenga me te tipu o ngā pūtau T, ka whakapai ake i te urupare ārai mate pukupuku, me te whakatutuki i ngā pānga ārai-pukupuku.
Kei raro i te arotake a te NMPA te NDA mō te ipilimumab me te sintilimab hei maimoatanga neoadjuvant mō te mate pukupuku koroni e kore e taea te tango i te microsatellite instability-high (MSI-H) me te mate pukupuku whakatikatika koretake (dMMR) rānei, ā, kua whakawhiwhia ki te tohu Arotake Matua.
Mō Sintilimab
Ko te Sintilimab, e hokohokohia ana ko TYVYT (werohanga sintilimab) i Haina, he paturopi monoclonal PD-1 immunoglobulin G4 i whakawhanakehia tahitia e Innovent me Eli Lilly and Company. Ko te Sintilimab he momo paturopi monoclonal immunoglobulin G4, e herea ana ki ngā ngota PD-1 i runga i te mata o ngā pūtau-T, e aukati ana i te ara PD-1 / PD-Ligand 1 (PD-L1), ā, e whakahohe ana i ngā pūtau-T ki te patu i ngā pūtau matepukupuku.
I tēnei wā, he maha tonu ngā whakamātautau haumanu o ngā hangarau hou hei ārai i te matepukupuku i Haina e rapu ana i ngā tūroro. Mēnā kei te hiahia koe ki te kōrero mō ngā rongoā me ngā hangarau hou, ka taea e koe te whakapā atu ki te Tari Ao o te Hōhipera Oncology Rohe Tonga o Beijing.
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Ngā Tohutoro
1.https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
Te wā tuku: 25-Pepuere-2025