Julaị 17, 2025 – Innovent Biologics kwupụtara na Nature Medicine ebipụtala nsonaazụ nke ọmụmụ ahụike nke Phase 1 nke IBI343, ihe ọhụrụ na-egbochi CLDN18.2 ADC, maka ọgwụgwọ nke adenocarcinoma afọ na-aga n'ihu (G/GEJ). Mbipụta na akwụkwọ agụmakwụkwọ mba ụwa a na-egosi nnabata siri ike nke ike ọgwụgwọ ahụ ma na-egosi ihe ọzọ dị mkpa na ọganihu China na imepụta ọgwụ mgbochi etuto ọhụrụ. Dabere na nchọpụta ọmụmụ ahụ, e hiwere nnwale ahụike nke Phase 3 nke mpaghara dị iche iche (G-HOPE-001, NCT06238843) na 2024 iji nyochaa IBI343 dị ka nhọrọ ọgwụgwọ dị nchebe ma dị irè maka ndị ọrịa nwere G/GEJ AC dị elu.
Ugbu a, enwere ọtụtụ nnwale ahụike nke teknụzụ ọhụrụ na-egbochi kansa na China na-achọ ndị ọrịa. Maka ndụmọdụ gbasara ọgwụ na teknụzụ ọhụrụ, ị nwere ike ịkpọtụrụ Ngalaba Mba Nile nke Ụlọ Ọgwụ Oncology nke Beijing South Region.
Nọmba ekwentị: 4008803716
WeChat ID: 17801183037
Ozi ịntanetị:myimmnet@163.com
Ọrịa kansa afọ ka bụ otu n'ime ọrịa kansa kachasị njọ n'ụwa. Dịka ọnụọgụgụ GLOBOCAN 2022 si kwuo, ọ bụ ọrịa kansa nke ise kachasị njọ na nke ise kachasị ebute ọnwụ metụtara ọrịa kansa n'ụwa niile, yana ihe dị ka ikpe ọhụrụ 970,000 na ọnwụ 660,000 kwa afọ. Kwa afọ, China na-akọ akụkọ ikpe ọhụrụ 359,000 na ọnwụ 260,000 site na ọrịa kansa afọ, nke na-anọchite anya 37.0% na 39.4% nke ngụkọta zuru ụwa ọnụ, n'otu n'otu, na-egosipụta mkpa ahụike dị ukwuu a na-emezughị.
CLDN 18.2 bụ protein njikọ siri ike nke a na-egosipụta n'ime mkpụrụ ndụ epithelial dị iche iche na mucosa afọ n'okpuru ọnọdụ ahụike nkịtị. Ọmụmụ ihe ndị gara aga egosila na Claudin18.2 na-egosipụta nke ọma n'ọtụtụ ụdị kansa, gụnyere kansa afọ (60-80%), kansa pancreas (50%), kansa esophageal (30-50%), na kansa akpa ume (40-60%). Iji CLDN18.2 mee ihe site na iji monoclonal antibodies (mAbs) na ADCs bụ ụzọ ọhụrụ dị mma maka ịgwọ kansa afọ.
Ọmụmụ ihe a ebipụtara bụ nnwale ahụike zuru ụwa ọnụ nke usoro nke mbụ (ClinicalTrial.gov identification: NCT05458219) nke e mere iji nyochaa nchekwa, ndidi na irè mbụ nke IBI343 n'ime ndị ọrịa nwere etuto siri ike dị elu. N'etiti Ọktoba 26, 2022, na June 30, 2024, e debanyere aha mmadụ 116 nwere adenocarcinoma G/GEJ dị elu iji nweta ọgwụgwọ IBI343 (8 na mmụba na mmụba na 108 na mmụba).
Banyere IBI343(Anti CLDN18.2 ADC)
IBI343 bụ ọgwụ mgbochi CLDN18.2 monoclonal antibody-drug conjugate (ADC) nke Innovent Biologics mepụtara. Ọ na-ejikọ kpọmkwem na mkpụrụ ndụ kansa nke na-egosipụta CLDN18.2, na-akpali CLDN18.2-dependent internalization nke ADC. Ozugbo ọ banyere n'ime mkpụrụ ndụ ahụ, a na-ahapụ ibu cytotoxic, na-ebute mmebi DNA na n'ikpeazụ apoptosis nke mkpụrụ ndụ kansa. Ọgwụ a tọhapụrụ nwekwara ike ịgbasa n'ofe plasma membrane iji ruo ma gbuo mkpụrụ ndụ ndị agbata obi, na-ebute "mmetụta igbu egbu site na mberede".
Dịka TOPO1i ADC ọhụrụ, IBI343 egosila nchekwa a na-anabata ma na-agba ume ka e jiri ya mee ihe n'ọmụmụ ihe gbasara ahụike nke Usoro 1 a. A na-enyocha ike ọgwụgwọ nke IBI343 ugbu a n'ụdị etuto ahụ dịka kansa afọ na kansa pancreatic.
Nnwale ahụike nke usoro nke atọ nke mpaghara dị iche iche nke IBI343 maka adenocarcinoma afọ na-aga n'ihu ugbu a na-akpọ ndị ọrịa (G-HOPE-001, NCT06238843). NMPA nke China enyela ihe ngosi dị mkpa maka Breakthrough Therapy Nomination (BTD).
Nnwale ahụike nke usoro nke mbụ nke IBI343 maka ọrịa kansa akwara nke pancreas dị elu na-edebakwa ndị ọrịa (NCT05458219). Ihe ngosi a enwetala aha Fast Track (FTD) site na US FDA ma NMPA nke China nyere ya BTD.
IBI343 egosila na ọ na-agba ume ka a gwọọ ọrịa kansa ma na-enyekwa aka ịlanarị ya.
Ọmụmụ ihe ahụ nyochachara data arụmọrụ nke ndị a na-enyocha nwere oke ngosipụta nke CLDN18.2 (≥75% mkpụrụ ndụ kansa nwere oke ntụpọ akpụkpọ ahụ ≥2+ site na IHC), n'ime otu ọgwụ abụọ nke 6 mg/kg na 8 mg/kg.
Na 6 mg/kg (N=31), ndị ọrịa 15 nwetara nzaghachi nke ọma (PR) gụnyere ndị ọrịa 9 nwere PR akwadoro na otu onye ọrịa na-eche nkwenye. ORR akwadoro bụ 29.0% (95% CI: 14.2-48.0) na ọnụego njikwa ọrịa (DCR) bụ 90.3% (95% CI: 74.2-98.0). Na ndị ọrịa 9 nwere nzaghachi akwadoro, oge nzaghachi etiti (DoR) bụ ọnwa 5.6 (95% CI: 2.8-7.0). Nlele etiti etiti bụ ọnwa 10.6 (95% CI: 9.7-11.5) maka PFS na OS. PFS etiti bụ ọnwa 5.5 (95% CI: 4.1-7.0). Data OS ezughị oke na OS etiti ugbu a nke ọnwa 10.8 (95% CI: 6.8-NC). Mgbe ewepụchara data ahụ, a kwadoro nzaghachi nke onye ọrịa 1 fọdụrụ na Julaị 26, 2024 ma melite ORR akwadoro ka ọ bụrụ 32.3% (95% CI: 16.7-51.4).
Na 8 mg/kg (N=17), a tụlere ndị ọrịa 17 nwere nnukwu ngosipụta nke CLDN 18.2. N'ime ha, ndị ọrịa 9 nwere PR gụnyere ndị ọrịa 8 egosila PR. ORR 47.1% (95% CI: 23.0-72.2) kwadoro, DCR bụkwa 88.2% (95% CI: 63.6-98.5). N'ime ndị ọrịa asatọ nwere ezigbo nzaghachi, etiti DoR bụ ọnwa 5.7 (95% CI: 2.7-NC). N'ime ndị ọrịa G/GEJ adenocarcinoma nwere nnukwu ngosipụta CLDN18.2 ejiri gwọọ na 8 mg/kg (N=19, gụnyere otu onye ọrịa site na mmụba dose na ndị ọrịa 18 site na mmụba dose), nleba anya etiti bụ ọnwa 8.1 (95% CI: 7.6-8.5) maka PFS na OS. Ọkwa PFS dị n'etiti bụ ọnwa 6.8 (95% CI: 2.8-7.5), a ruteghịkwa sistemụ arụmọrụ etiti ahụ mgbe ihe merenụ mere na ndị ọrịa 36.8%.
IBI343 gosikwara nchekwa dị elu
N'ime ndị ọrịa niile nwere G/GEJ adenocarcinoma (n=116, gụnyere ndị ọrịa asatọ nwere kansa afọ site na usoro mmụba dose), ndị ọrịa 66.4% (77/116) nwere TEAE ọkwa ≥3. Ọnụọgụ neutrophil kachasị ≥3 (≥35%) belatara (28.4%), ọnụọgụ mkpụrụ ndụ ọbara ọcha belatara (25.9%), na ọbara ọgbụgba (16.4%). E nwere obere ihe ọghọm afọ nke ọkwa ≥3, gụnyere naanị 1.7% nke ọgbụgbọ ọkwa ≥3. A kọghị ọrịa akpa ume n'etiti ọkwa ọ bụla. E belatara nsí metụtara ọgwụgwọ site na ọgwụgwọ nkwado zuru oke, nchekwa zuru oke dịkwa mma.
Ugbu a, enwere ọtụtụ nnwale ahụike nke teknụzụ ọhụrụ na-egbochi kansa na China na-achọ ndị ọrịa. Maka ndụmọdụ gbasara ọgwụ na teknụzụ ọhụrụ, ị nwere ike ịkpọtụrụ Ngalaba Mba Nile nke Ụlọ Ọgwụ Oncology nke Beijing South Region.
Nọmba ekwentị: 4008803716
WeChat ID: 17801183037
Ozi ịntanetị:myimmnet@163.com
Oge ozi: Julaị-22-2025