ʻO SHR-A1904, kahi CLDN18.2-Targeting ADC, Hōʻike i ka Hana Anti-Tumor i ka Holomua ʻana o ka Gastric/Gastroesophageal Junction Cancer: Nā Hualoaʻa o ka Hoʻāʻo ʻana o ka Pae 1

Ma Iulai 16, ua paʻi ka puke pai honua kiʻekiʻe ʻo Nature Medicine i ka ʻikepili noiʻi ma SHR-A1904, kahi antibody-drug conjugate (ADC) e kuhikuhi ana iā claudin 18.2 (CLDN18.2), no ka mālama ʻana i ka maʻi ʻaʻai gastric holomua a i ʻole ka maʻi ʻaʻai gastroesophageal junction (GC/GEJC). Ua hana nā mea noiʻi i kahi hoʻokolohua lapaʻau mua-i-kanaka, ʻekolu-paepae, Phase 1 e loiloi i ka pono o SHR-A1904 i 95 mau maʻi i mālama mua ʻia me ka maʻi ʻaʻai G/GEJ holomua CLDN18.2-positive.

I kēia manawa, nui nā hoʻokolohua lapaʻau o nā ʻenehana anti-cancer hou ma Kina e ʻimi nei i nā maʻi. I ke kūkākūkā ʻana i nā lāʻau lapaʻau a me nā ʻenehana hou, hiki iā ʻoe ke hoʻokaʻaʻike aku i ka Beijing South Region Oncology Hospital International Department.

Helu Kelepona：4008803716

ʻIkepili WeChat: 17801183037

Email：myimmnet@163.com

ʻO Claudin-18 isoform 2 (CLDN18.2), kahi protein tight junction i hōʻike ʻia i loko o ka epithelium gastric non-malignant a hōʻike ʻia ma ka ʻili o nā cell tumor i ka wā o ka hoʻololi malignant, he pahuhopu therapeutic hoʻohiki no nā maʻi ʻaʻai gastric a me gastroesophageal junction (G/GEJ). ʻO SHR-A1904 kahi antibody-drug conjugate e loaʻa ana ka CLDN18.2-targeting monoclonal antibody, kahi DNA topoisomerase I inhibitor payload a me kahi peptide-based linker cleavable.

I ke kahua hoʻonui nui ʻana o ka lāʻau (0.6–8.0 mg kg−1), ua ʻike ʻia nā ʻawaʻawa palena lāʻau i ʻelua mau maʻi ma 4.8 mg kg−1 (ʻo ka neutropenia febrile papa 3 a me ka bilirubin koko i hoʻonui ʻia i ka papa 3) a ma kekahi maʻi ma 6.0 mg kg−1 (ʻeha mucosal gastric papa 3). ʻAʻole i hiki i ka nui o ka lāʻau i ʻae ʻia, a ua koho ʻia ʻo 6.0 mg kg−1 a me 8.0 mg kg−1 no ka hoʻonui ʻana i ka pharmacokinetic a me ka pono. Ua loaʻa nā hanana ʻino i ka lāʻau lapaʻau i nā maʻi 95 a pau, ʻo ka hapa nui o ka anemia (72 (75.8%)), ka nausea (64 (67.4%)), hypoalbuminemia (61 (64.2%)) a me ka emi ʻana o ka helu o nā cell koko keʻokeʻo (56 (58.9%)). Eia kekahi, ua loaʻa i nā maʻi 59 (62.1%) nā hanana ʻino e pili ana i ka lāʻau lapaʻau papa 3 a ʻoi aku paha. ʻAʻohe make e pili ana i ka lāʻau i hōʻike ʻia. Ma waena o nā poʻe maʻi i hiki ke loiloi ʻia ka pane, ʻo ka helu pane i hōʻoia ʻia he 24.2% (95% interval hilinaʻi (CI), 11.1–42.3) ma 6.0 mg kg−1 a me 25.0% (95% CI, 12.1–42.2) ma 8.0 mg kg−1. ʻO ke ola waena me ka ʻole o ka holomua he 5.6 mau mahina (95% CI, 3.0–6.9) ma 6.0 mg kg−1 a me 5.8 mau mahina (95% CI, 3.0–8.6) ma 8.0 mg kg−1. I ka hopena, ua hōʻike ʻo SHR-A1904 i kahi ʻano palekana hiki ke hoʻokele ʻia a me ka paipai ʻana i ka hana anti-tumor i nā poʻe maʻi me ka maʻi ʻaʻai G/GEJ CLDN18.2-positive, e pono ai ka noiʻi hou aku.

I kēia manawa, nui nā hoʻokolohua lapaʻau o nā ʻenehana anti-cancer hou ma Kina e ʻimi nei i nā maʻi. I ke kūkākūkā ʻana i nā lāʻau lapaʻau a me nā ʻenehana hou, hiki iā ʻoe ke hoʻokaʻaʻike aku i ka Beijing South Region Oncology Hospital International Department.

Helu Kelepona：4008803716

ʻIkepili WeChat: 17801183037

Email：myimmnet@163.com