Chikunguru 17, 2025 - Innovent Biologics yakazivisa kuti Nature Medicine yakaburitsa mhedzisiro yechidzidzo chekiriniki chePhase 1 cheIBI343, mushonga mutsva wekurwisa CLDN18.2 ADC, wekurapa advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Kuburitswa mumagazini iyi yedzidzo yepasi rose kunoratidza kuzivikanwa kwakasimba kwehunyanzvi hwekurapa uye kunoratidza chimwe chiitiko chakakosha mukufambira mberi kweChina mukugadzira mishonga mitsva yekurwisa bundu. Zvichibva pane zvakawanikwa muchidzidzo ichi, bvunzo yekiriniki yePhase 3 yematunhu akawanda (G-HOPE-001, NCT06238843) yakatangwa muna 2024 kuti iongorore zvakare IBI343 senzira yekurapa yakachengeteka uye inoshanda kune varwere vane G/GEJ AC yepamusoro.
Parizvino, kuchine miedzo yakawanda yekiriniki yehunyanzvi hutsva hwekurwisa gomarara muChina huri kutsvaga varwere. Kana muchida kubvunzana nezvemishonga mitsva netekinoroji, munogona kubata Dhipatimendi reBeijing South Region Oncology Hospital International.
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Gomarara remudumbu richiri rimwe remagomarara anonyanya kupararira pasi rose. Sekureva kwehuwandu hweGLOBOCAN 2022, riri pachinzvimbo chechishanu pakukura kwegomarara remudumbu uye pachinzvimbo chechishanu pakukura kwerufu runokonzerwa negomarara pasi rose, nezvirwere zvitsva zvinofungidzirwa kuti 970,000 uye 660,000 pagore. Gore rega rega, China inoshuma zviitiko zvitsva 359,000 uye 260,000 vakafa negomarara remudumbu, zvichireva 37.0% uye 39.4% yehuwandu hwese hwepasi rose, zvichiratidza kuti pane zvinodiwa zvehutano zvisina kuzadzikiswa.
CLDN 18.2 ipuroteni ine tight junction inoratidzwa mumasero e epithelial akasiyana-siyana ari padumbu pasi pemamiriro ezvinhu akajairwa emuviri. Ongororo dzakapfuura dzakaratidza kuti Claudin18.2 inoratidzwa zvakanyanya mumhando dzakasiyana dzekenza, kusanganisira kenza yemudumbu (60-80%), kenza yepancreatic (50%), esophageal carcinoma (30-50%), uye kenza yemapapu (40-60%). Kutarisa CLDN18.2 ne monoclonal antibodies (mAbs) neADCs inzira itsva inovimbisa yekurapa kenza yemudumbu.
Chidzidzo ichi chakaburitswa iongororo yepasi rose, ine nzvimbo dzakawanda dzekurapa muchikamu chekutanga (ClinicalTrial.gov identifier: NCT05458219) yakagadzirirwa kuongorora kuchengetedzeka, kushivirira uye kushanda kwekutanga kweIBI343 muvarwere vane bundu rakasimba. Pakati paGumiguru 26, 2022, naChikumi 30, 2024, vanhu vanosvika zana negumi nevatanhatu vane G/GEJ adenocarcinoma yepamusoro vakanyoreswa kuti vagamuchire IBI343 monotherapy (8 iri kuwedzera uye 108 iri kuwedzera).
Nezve IBI343 (Anti CLDN18.2 ADC)
IBI343 imushonga wekudzivirira mabhakitiriya wevanhu unodzivirira CLDN18.2 monoclonal antibody-drug conjugate (ADC) wakagadzirwa neInnovent Biologics. Unonyatsobatana nemasero ekenza ane CLDN18.2, zvichikonzera CLDN18.2-dependent internalization yeADC. Kana wangopinda musero, cytotoxic payload inoburitswa, zvichikonzera kukuvara kweDNA uye pakupedzisira apoptosis yemasero ekenza. Mushonga unoburitswa unogona zvakare kupararira neplasma membrane kuti usvike nekuuraya masero ari pedyo, zvichikonzera "kuuraya kwemunhu ari pedyo".
Semushonga mutsva weTOPO1i ADC, IBI343 yakaratidza kuchengetedzeka kunoshivirira uye kukurudzira zviratidzo zvinoshanda muzvidzidzo zvekiriniki zvePase 1. Kugona kwekurapa kweIBI343 kuri kuongororwa pari zvino mumhando dzemabundu akadai sekenza yemudumbu nekenza yepancreas.
Kuedzwa kwekiriniki kwechikamu chechitatu chechikamu chezvikamu zvakasiyana-siyana kweIBI343 kweadenocarcinoma yemudumbu/gastroesophageal junction kuri kutora varwere (G-HOPE-001, NCT06238843). Chiratidzo chakakodzera chakapihwa Breakthrough Therapy Designation (BTD) neNMPA yeChina.
Kuedzwa kwekiriniki kwechikamu chekutanga cheIBI343 mumatunhu akawanda ePase 1 yekurapa adenocarcinoma yepancreatic iri kunyoresawo varwere (NCT05458219). Chiratidzo ichi chakapihwa Fast Track Designation (FTD) kubva kuUS FDA uye chakapihwa BTD neNMPA yeChina.
IBI343 yakaratidza kukurudzira kupindura kwegomarara uye kubatsira kwekurarama.
Chidzidzo ichi chakaongorora ruzivo rwekushanda kwevanhu vanoongororwa vane CLDN18.2 yakawanda (≥75% masero egomarara ane simba rekutsvedza kweganda ≥2+ neIHC), mumapoka maviri e6 mg/kg uye 8 mg/kg.
Pa6 mg/kg (N=31), varwere gumi nevashanu vakapindura zvishoma (PR) kusanganisira varwere vapfumbamwe vane PR dzakasimbiswa uye murwere mumwe chete akamirira kusimbiswa. ORR yakasimbiswa yaive 29.0% (95% CI: 14.2-48.0) uye chiyero chekutonga chirwere (DCR) chaive 90.3% (95% CI: 74.2-98.0). Muvarwere vapfumbamwe vane mhinduro yakasimbiswa, nguva yepakati yemhinduro (DoR) yaive mwedzi 5.6 (95% CI: 2.8-7.0). Kutevera kwepakati kwaive kwemwedzi 10.6 (95% CI: 9.7-11.5) yePFS neOS. PFS yepakati yaive mwedzi 5.5 (95% CI: 4.1-7.0). Data reOS harina kukura neOS yepakati yemwedzi 10.8 (95% CI: 6.8-NC). Mushure mekuchekwa kwedata, mhinduro yemurwere mumwe chete yakasimbiswa musi wa26 Chikunguru, 2024 uye ORR yakasimbiswa yakagadziridzwa kusvika pa32.3% (95% CI: 16.7-51.4).
Pa 8 mg/kg (N=17), varwere gumi nevanomwe vane CLDN 18.2 yakanyanya kuratidzwa vakaongororwa. Pakati pavo, varwere vapfumbamwe vaiva nePRs kusanganisira varwere vasere vakanga varatidza PR. ORR yakasimbiswa 47.1% (95% CI: 23.0-72.2), uye DCR yaive 88.2% (95% CI: 63.6-98.5). Muvarwere vasere vane mhinduro yakasimbiswa, avhareji yeDoR yaive mwedzi 5.7 (95% CI: 2.7-NC). Pavarwere vese veG/GEJ adenocarcinoma vane CLDN18.2 yakanyanya kuratidzwa vakarapwa pa 8 mg/kg (N=19, kusanganisira murwere mumwe chete kubva pakuwedzerwa kwedosi uye varwere gumi nevasere kubva pakuwedzerwa kwedosi), avhareji yekutevera yaive mwedzi 8.1 (95% CI: 7.6-8.5) yePFS neOS. PFS yepakati yaive mwedzi 6.8 (95% CI: 2.8-7.5), uye OS yepakati haina kusvikwa nezviitiko zvakaitika mu36.8% yevarwere.
IBI343 yakaratidzawo kuchengetedzeka kwakanyanya
Pakati pevarwere vese vane G/GEJ adenocarcinoma (n=116, kusanganisira varwere vasere vane kenza yemudumbu kubva padanho rekuwedzera dose), varwere 66.4% (77/116) vaive neTEAE dzegiredhi ≥3. MaTEAE egiredhi ≥3 akajairika (≥35%) aive nenhamba ye neutrophil yakaderera (28.4%), nhamba yemasero machena eropa yakaderera (25.9%), uye anemia (16.4%). Paive nezviitiko zvishoma zvematambudziko emudumbu zvegiredhi ≥3, kusanganisira 1.7% chete yekuda kurutsa kwegiredhi ≥3. Hapana chirwere chemukati memapapu chero chipi zvacho chakataurwa. Chepfu yakabatana nekurapwa yakaderedzwa nekurapwa kwakaringana, uye kuchengetedzeka kwacho kwaigoneka.
Parizvino, kuchine miedzo yakawanda yekiriniki yehunyanzvi hutsva hwekurwisa gomarara muChina huri kutsvaga varwere. Kana muchida kubvunzana nezvemishonga mitsva netekinoroji, munogona kubata Dhipatimendi reBeijing South Region Oncology Hospital International.
Nhamba yefoni: 4008803716
Nhamba yeWeChat: 17801183037
Imeyili：myimmnet@163.com
Nguva yekutumira: Chikunguru-22-2025