NMPA Txais NDA thiab Muab Kev Tshuaj Xyuas Ua Ntej rau Innovent's Ipilimumab Txhaj Tshuaj, Tuam Tshoj thawj zaug CTLA-4 Inhibitor hauv tebchaws, ua ke nrog Sintilimab ua Neoadjuvant Kev Kho Mob rau Mob Cancer Colon

Thaum Lub Ob Hlis 22, 2025, Daim Ntawv Thov Tshuaj Tshiab (NDA) rau kev txhaj tshuaj ipilimumab (anti-CTLA-4 monoclonal antibody; R&D Code: IBI310) tau txais los ntawm Lub Chaw Saib Xyuas Kev Tshuaj Xyuas Tshuaj (CDE) ntawm Tuam Tshoj Lub Chaw Tswj Xyuas Khoom Siv Kho Mob Hauv Tebchaws (NMPA) thiab tau txais kev tshuaj xyuas ua ntej ua ke nrog sintilimab ua kev kho mob neoadjuvant rau kev phais mob microsatellite instability-high (MSI-H) lossis mismatch repair deficient (dMMR) mob qog noj ntshav hauv plab hnyuv.

Qhov no yog thawj NDA hauv Suav teb rau cov tshuaj CTLA-4 inhibitor hauv tebchaws thiab lwm qhov tseem ceeb uas ua rau sintilimab muaj zog ua tus thawj coj hauv kev kho mob qog noj ntshav. Kev kho mob Immune checkpoint blockade (ICB) uas tsom mus rau PD-1 thiab CTLA-4 tau hloov pauv kev kho mob oncology, ipilimumab nrog sintilimab ua kev kho mob neoadjuvant tuaj yeem ua rau R0 resection rate nce ntxiv, ua tiav kev teb tiav, thiab txo cov neeg mob feem ntau ntawm cov teeb meem chemotherapy adjuvant. Kev kho mob tshiab no kuj xav tias yuav txo qhov rov tshwm sim thiab txhim kho kev kwv yees mus sij hawm ntev, xav tias yuav pab tau cov neeg mob qog noj ntshav MSI-H/dMMR thaum NDA pom zoo.

Kev lees txais NDA thiab Kev Tshuaj Xyuas Ua Ntej yog raws li cov txiaj ntsig los ntawm kev sim tshuaj theem 3 uas tau xaiv los ntawm ntau lub chaw, ntau lub chaw, thiab tseem ceeb (NeoShot, NCT05890742) uas tau soj ntsuam qhov kev nyab xeeb thiab kev ua tau zoo ntawm ipilimumab ua ke nrog sintilimab ua kev kho mob neoadjuvant thiab piv rau kev phais mob ncaj qha rau mob qog noj ntshav hauv plab hnyuv MSI-H/dMMR. Cov ntsiab lus tseem ceeb yog qhov kev teb tiav ntawm cov kab mob (pCR) thiab kev ciaj sia tsis muaj xwm txheej (EFS). Kev tshuaj xyuas ib ntus los ntawm Pawg Neeg Saib Xyuas Cov Ntaub Ntawv Ywj Pheej (IDMC) tau qhia tias kev sim tshuaj NeoShot tau ua tiav nws qhov kawg tseem ceeb.

Txij li thaum Lub Ob Hlis 4, 2024, muaj 101 pts tau sau npe (txiv neej: 55.4%, hnub nyoog nruab nrab: 56 xyoo, ECOG PS 1: 54.5%, muaj kev pheej hmoo siab: 76.2%) thiab tau xaiv mus rau hauv caj npab A (n = 52) thiab caj npab B (n = 49). Hauv caj npab A, 1 pt tau xaus kev kho mob ntxov (rho tawm). Hauv caj npab B, 4 pts tau xaus kev kho mob ntxov (1 rho tawm, 1 tuag, 2 txuas ntxiv neoadjuvant sintilimab). Kev phais mob raws sijhawm tau ua tiav hauv 51 (98.1%) cov qhab nia hauv caj npab A thiab 45 (91.8%) cov qhab nia hauv caj npab B. Kev ntsuam xyuas tom qab phais tau qhia txog kev kho tsis sib xws (pMMR) hauv 1 qhab nia txhua tus hauv caj npab A thiab caj npab B. Cov nqi pCR yog 80.0% (40/50, 95%CI: 66.3-90.0) hauv caj npab A piv rau 47.7% (21/44, 95%CI: 32.5-63.3) hauv caj npab B (p = 0.0007). Txhua tus qhab nia tau txais kev phais muaj R0 resection. Lub sijhawm nruab nrab ntawm thawj koob tshuaj ntawm kev kho mob neoadjuvant thiab kev phais yog 47 hnub (ntau yam: 35-82). Kev phais mob qeeb tau tshwm sim hauv 3 pts suav nrog 2 pts hauv caj npab A vim yog qib 2 hypothyroidism (qeeb 2 hnub) thiab qib 1 hyperthyroidism (qeeb 13 hnub), thiab 1 pt hauv caj npab B rau lwm yam laj thawj (qeeb 26 hnub). Cov xwm txheej tsis zoo uas tshwm sim los ntawm kev kho mob (TEAEs) tau tshwm sim hauv 46 pts (88.5%, qib ≥3 hauv 13 pts) hauv caj npab A thiab 39 pts (79.6%, qib ≥3 hauv 9 pts) hauv caj npab B. Cov xwm txheej tsis zoo uas cuam tshuam nrog kev tiv thaiv kab mob (irAEs) tau tshwm sim hauv 22 pts (42.3%) hauv caj npab A thiab 18 pts (36.7%) hauv caj npab B. Qib ≥3 irAEs tau tshwm sim hauv 3 pts hauv caj npab A, suav nrog kev tiv thaiv kab mob myocarditis, ileus thiab enteritis, thiab hauv 4 pts hauv caj npab B, suav nrog alanine aminotransferase nce ntxiv, pob khaus, hypothyroidism thiab myocarditis. Muaj TRAEs loj heev tshwm sim hauv 4 (7.7%) pts hauv caj npab A thiab 3 (6.1%) pts hauv caj npab B. TRAE ua rau tuag tau tshwm sim hauv 1 pt hauv caj npab B (myocarditis).

Txog Ipilimumab

Ipilimumab (R&D code: IBI310) yog ib qho tshuaj monoclonal antibody uas tsim los ntawm Innovent. Ipilimumab muaj peev xwm khi cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), yog li ntawd thaiv CTLA-4 mediated T cell inhibition, txhawb T cell activation thiab proliferation, txhim kho kev tiv thaiv kab mob qog noj ntshav, thiab ua tiav cov teebmeem tiv thaiv qog noj ntshav.

Lub NDA rau ipilimumab ua ke nrog sintilimab ua kev kho mob neoadjuvant rau kev phais mob microsatellite instability-high (MSI-H) lossis mismatch repair deficient (dMMR) mob qog nqaij hlav plab hnyuv yog nyob rau hauv NMPA kev tshuaj xyuas thiab tau txais kev tso cai Priority Review.

Txog Sintilimab

Sintilimab, muag raws li TYVYT (sintilimab txhaj tshuaj) hauv Suav teb, yog PD-1 immunoglobulin G4 monoclonal antibody uas tau tsim los ntawm Innovent thiab Eli Lilly thiab Company. Sintilimab yog ib hom immunoglobulin G4 monoclonal antibody, uas khi rau PD-1 molecules ntawm qhov chaw ntawm T-cells, thaiv txoj kev PD-1 / PD-Ligand 1 (PD-L1), thiab rov ua kom T-cells rov ua haujlwm los tua cov hlwb qog noj ntshav.

Tam sim no, tseem muaj ntau qhov kev sim tshuaj kho mob qog noj ntshav tshiab hauv Suav teb nrhiav cov neeg mob. Kev sab laj txog cov tshuaj tshiab thiab cov thev naus laus zis, koj tuaj yeem tiv tauj Beijing South Region Oncology Hospital International Department.

Xov Tooj: 4008803716

Email：myimmnet@163.com

Cov ntaub ntawv siv los ua piv txwv

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

2.Kev kho mob Neoadjuvant ntawm IBI310 (anti-CTLA-4 antibody) ntxiv rau sintilimab (anti-PD-1 antibody) rau cov neeg mob uas muaj mob qog nqaij hlav colorectal tsis ruaj khov-siab / tsis sib xws kho-tsis zoo: Cov txiaj ntsig los ntawm kev tshawb fawb randomized, qhib-labeled, theem Ib. | Journal of Clinical Oncology (ascopubs.org)

3.信达生物 (innoventbio.com)