Ka la 22 Hlakola 2025, Kopo e Ncha ea Meriana (NDA) bakeng sa ente ea ipilimumab (anti-CTLA-4 monoclonal antibody; Khoutu ea R&D: IBI310) e amohetsoe ke Setsi sa Tlhahlobo ea Meriana (CDE) sa Tsamaiso ea Naha ea Lihlahisoa tsa Bongaka ea Chaena (NMPA) 'me sa fuoa Priority Review title hammoho le sintilimab e le kalafo ea neoadjuvant bakeng sa kankere ea mala e ka senngoang ea microsatellite instability-high (MSI-H) kapa mismatch repair deficient (dMMR).
Ena ke NDA ea pele ea Chaena bakeng sa thibelo ea CTLA-4 ea lapeng le ketsahalo e 'ngoe ea bohlokoa e matlafatsang boemo ba boetapele ba sintilimab kalafong ea mofetše. Kalafo ea thibelo ea 'mele ea ho itšireletsa mafung (ICB) e shebaneng le PD-1 le CTLA-4 e fetotse kalafo ea oncology, ipilimumab ka sintilimab e le kalafo ea neoadjuvant e ka eketsa sekhahla sa ho tlosoa ha R0, ea fihlela karabelo e felletseng ea pathological, le ho imolla bakuli ba bangata moroalong oa chemotherapy ea adjuvant. Kalafo ena e ncha e boetse e lebelletsoe ho fokotsa sekhahla sa ho khutla hape le ho ntlafatsa tebello ea nako e telele, e lebelletsoeng ho thusa bakuli ba mofetše oa mala a maholo oa MSI-H/dMMR ha NDA e amoheloa.
Kamohelo ea NDA le Tlhahlobo ea Bohlokoa li ipapisitse le liphetho tse tsoang tekong ea bongaka ea Mokhahlelo oa 3 e sa reroang, e laoloang, e nang le litsi tse ngata, e bohlokoa (NeoShot, NCT05890742) e ileng ea hlahloba polokeho le katleho ea ipilimumab e kopantsoeng le sintilimab e le phekolo ea neoadjuvant le ha e bapisoa le opereishene e tobileng ea radical bakeng sa kankere ea mala a maholo ea MSI-H/dMMR. Liphetho tsa mantlha ke sekhahla sa karabelo e felletseng ea pathologic (pCR) le ho pholoha ntle le liketsahalo (EFS). Tlhahlobo ea nakoana ke Komiti e Ikemetseng ea Tlhokomelo ea Lintlha (IDMC) e bontšitse hore teko ea NeoShot e fihletse pheletso ea eona ea mantlha.
Ho tloha ka la 4 Hlakola 2024, ho ile ha ngolisoa batho ba 101 (banna: 55.4%, lilemo tse mahareng: lilemo tse 56, ECOG PS 1: 54.5%, kotsi e kholo: 76.2%) 'me ea kenngoa ka mokhoa o sa reroang ho A (n = 52) le B (n = 49). Letsohong la A, motho a le mong o ile a khaotsa kalafo pele ho nako (a khaotsa). Letsohong la B, batho ba 4 ba ile ba khaotsa kalafo pele ho nako (a khaotsa a le mong, a hlokahala a le mong, ba 2 ba ile ba tsoela pele ka neoadjuvant sintilimab). Ho sehoa ha phekolo ho reriloeng ho entsoe ka lintlha tse 51 (98.1%) letsohong A le lintlha tse 45 (91.8%) letsohong B. Tlhahlobo ea kamora opereishene e senotse hore ho na le bokhoni ba ho lokisa bo sa tsamaellaneng (pMMR) ka ntlha e le 'ngoe letsohong A le letsoho B. Sekhahla sa pCR e ne e le 80.0% (40/50, 95%CI: 66.3-90.0) letsohong A khahlanong le 47.7% (21/44, 95%CI: 32.5-63.3) letsohong B (p = 0.0007). Lintlha tsohle tse ileng tsa etsoa opereishene li ne li e-na le ho sehoa ha R0. Nako e mahareng pakeng tsa tekanyo ea pele ea kalafo ea neoadjuvant le opereishene e ne e le matsatsi a 47 (sebaka: 35-82). Tieho ea opereishene e etsahetse ka makhetlo a 3 ho kenyeletsoa lintlha tse 2 letsohong A ka lebaka la hypothyroidism ea sehlopha sa 2 (tieho ea matsatsi a 2) le hyperthyroidism ea sehlopha sa 1 (tieho ea matsatsi a 13), le ntlha e le 'ngoe letsohong B ka lebaka le leng (tieho ea matsatsi a 26). Liketsahalo tse mpe tse hlahang ka kalafo (TEAEs) li etsahetse ka makhetlo a 46 (88.5%, sehlopha≥3 ka makhetlo a 13) letsohong A le lintlha tse 39 (79.6%, sehlopha≥3 ka makhetlo a 9) letsohong B. Liketsahalo tse mpe tse amanang le 'mele oa ho itšireletsa mafung (irAEs) li etsahetse ka makhetlo a 22 (42.3%) letsohong A le lintlha tse 18 (36.7%) letsohong B. Li-irAE tsa sehlopha sa ≥3 li etsahetse ka makhetlo a 3 letsohong A, ho kenyeletsoa le myocarditis e bakoang ke 'mele, ileus le enteritis, le ka makhetlo a 4 letsohong B, ho kenyeletsoa le alanine aminotransferase e eketsehileng, lekhopho, hypothyroidism le myocarditis. Li-TRAE tse tebileng li etsahetse ka lintlha tse 4 (7.7%) letsohong la A le lintlha tse 3 (6.1%) letsohong la B. TRAE e lebisang lefung e etsahetse ka lintlha tse 1 letsohong la B (myocarditis).
Mabapi le Ipilimumab
Ipilimumab (Khoutu ea R&D: IBI310) ke ente ea antibody ea monoclonal e entsoeng ka boikemelo ke Innovent. Ipilimumab e ka tlama antigen 4 (CTLA-4) e amanang le cytotoxic cytotoxic T lymphocyte ka ho khetheha, ka hona e thibela thibelo ea lisele tsa T tse tsamaisoang ke CTLA-4, e khothalletsa ts'ebetso ea lisele tsa T le ho ata ha tsona, e ntlafatsa karabelo ea 'mele ea ho itšireletsa mafung, le ho fihlela litlamorao tsa ho loantša hlahala.
NDA bakeng sa ipilimumab hammoho le sintilimab e le kalafo ea neoadjuvant bakeng sa kankere ea mala e nang le ho se sebetse hantle ha microsatellite (MSI-H) kapa ho se sebetse hantle ha repair deficient (dMMR) e tlas'a tlhahlobo ea NMPA 'me e filoe Priority Review title.
Mabapi le Sintilimab
Sintilimab, e rekisoang e le TYVYT (ente ea sintilimab) Chaena, ke antibody ea PD-1 immunoglobulin G4 monoclonal e ntlafalitsoeng hammoho ke Innovent le Eli Lilly and Company. Sintilimab ke mofuta oa antibody ea immunoglobulin G4 monoclonal, e tlamang limolek'hule tsa PD-1 holim'a lisele tsa T, e thibela tsela ea PD-1 / PD-Ligand 1 (PD-L1), 'me e tsosolosa lisele tsa T ho bolaea lisele tsa mofetše.
Hona jwale, ho ntse ho na le diteko tse ngata tsa bongaka tsa mahlale a matjha a ho lwantsha kankere Chaena a batlang bakudi. Dipuisano mabapi le meriana le mahlale a matjha, o ka ikopanya le Lefapha la Matjhaba la Sepetlele sa Oncology sa Beijing Region South.
Nomoro ea mohala: 4008803716
Email：myimmnet@163.com
Litšupiso
1.https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
Nako ea poso: Hlakola-25-2025