Lub Xya Hli 17, 2025 – Innovent Biologics tshaj tawm tias Nature Medicine tau tshaj tawm cov txiaj ntsig ntawm Kev Tshawb Fawb Txog Kev Kho Mob Theem 1 ntawm IBI343, uas yog ib qho tshuaj anti-CLDN18.2 ADC tshiab, rau kev kho mob qog nqaij hlav gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Kev tshaj tawm hauv phau ntawv xov xwm kev kawm thoob ntiaj teb no qhia txog kev lees paub zoo txog lub peev xwm kho mob ntawm kev kho mob thiab yog ib qho tseem ceeb rau kev vam meej ntawm Tuam Tshoj hauv kev tsim cov tshuaj tiv thaiv qog nqaij hlav tshiab. Raws li cov ntaub ntawv tshawb pom, kev sim tshuaj theem 3 ntau cheeb tsam (G-HOPE-001, NCT06238843) tau pib xyoo 2024 los soj ntsuam ntxiv txog IBI343 ua ib qho kev xaiv kho mob zoo thiab muaj txiaj ntsig rau cov neeg mob uas muaj G/GEJ AC siab heev.
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.
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Kab mob qog nqaij hlav hauv plab tseem yog ib qho ntawm cov qog nqaij hlav phem tshaj plaws hauv ntiaj teb. Raws li cov ntaub ntawv GLOBOCAN 2022, nws yog qhov qog nqaij hlav phem thib tsib thiab qhov thib tsib ua rau muaj kev tuag los ntawm kab mob qog nqaij hlav thoob ntiaj teb, nrog kwv yees li ntawm 970,000 tus neeg mob tshiab thiab 660,000 tus neeg tuag txhua xyoo. Txhua xyoo, Tuam Tshoj tshaj tawm txog 359,000 tus neeg mob tshiab thiab 260,000 tus neeg tuag los ntawm kab mob qog nqaij hlav hauv plab, uas sawv cev rau 37.0% thiab 39.4% ntawm tag nrho thoob ntiaj teb, raws li, qhia txog qhov xav tau kev kho mob tseem ceeb uas tsis tau txais kev pab.
CLDN 18.2 yog ib qho protein sib txuas nruj uas qhia tawm hauv cov hlwb epithelial sib txawv ntawm lub plab zom mov hauv qab cov mob ib txwm muaj. Cov kev tshawb fawb yav dhau los tau qhia tias Claudin18.2 tau qhia tawm ntau yam hauv ntau hom mob qog noj ntshav, suav nrog mob qog noj ntshav hauv plab (60-80%), mob qog noj ntshav pancreatic (50%), mob qog noj ntshav esophageal (30-50%), thiab mob qog noj ntshav ntsws (40-60%). Kev tsom mus rau CLDN18.2 nrog cov tshuaj monoclonal antibodies (mAbs) thiab ADCs sawv cev rau txoj hauv kev tshiab zoo rau kev kho mob qog noj ntshav hauv plab.
Daim kev tshawb fawb no yog kev sim tshuaj thoob ntiaj teb, ntau lub chaw, theem 1 (ClinicalTrial.gov tus cim: NCT05458219) uas tsim los ntsuam xyuas kev nyab xeeb, kev kam rau siab thiab kev ua haujlwm zoo ntawm IBI343 rau cov neeg mob uas muaj cov qog nqaij hlav loj hlob. Nruab nrab ntawm lub Kaum Hli 26, 2022, thiab Lub Rau Hli 30, 2024, tag nrho ntawm 116 tus neeg mob uas muaj G/GEJ adenocarcinoma siab heev tau sau npe kom tau txais IBI343 monotherapy (8 hauv kev nce qib thiab 108 hauv kev nthuav dav).
Txog IBI343 (Anti CLDN18.2 ADC)
IBI343 yog ib qho tshuaj recombinant human anti-CLDN18.2 monoclonal antibody-drug conjugate (ADC) uas tsim los ntawm Innovent Biologics. Nws khi rau cov hlwb qog nqaij hlav uas qhia CLDN18.2, ua rau CLDN18.2-dependent internalization ntawm ADC. Thaum nkag mus rau hauv lub hlwb, cov cytotoxic payload raug tso tawm, ua rau DNA puas tsuaj thiab thaum kawg apoptosis ntawm cov hlwb qog nqaij hlav. Cov tshuaj uas tso tawm kuj tuaj yeem kis mus thoob plaws hauv plasma membrane kom mus txog thiab tua cov hlwb nyob ze, ua rau muaj "bystander killing effect".
Ua ib qho TOPO1i ADC tshiab, IBI343 tau ua pov thawj tias muaj kev nyab xeeb thiab txhawb nqa cov cim qhia txog kev ua haujlwm zoo hauv kev tshawb fawb theem 1 no. Lub peev xwm kho mob ntawm IBI343 tam sim no tab tom tshawb nrhiav hauv cov hom qog xws li mob qog noj ntshav hauv plab thiab mob qog noj ntshav hauv pancreatic.
Qhov kev sim tshuaj kho mob theem 3 ntawm ntau thaj tsam ntawm IBI343 rau kev mob qog nqaij hlav gastric / gastroesophageal junction adenocarcinoma tam sim no tab tom nrhiav cov neeg mob (G-HOPE-001, NCT06238843). Cov cim qhia tseem ceeb tau txais Breakthrough Therapy Designation (BTD) los ntawm NMPA ntawm Tuam Tshoj.
Qhov kev sim tshuaj IBI343 theem 1 uas siv ntau thaj tsam rau kev kho mob qog nqaij hlav pancreatic ductal adenocarcinoma kuj tau txais cov neeg mob (NCT05458219). Qhov cim qhia no tau txais Fast Track Designation (FTD) los ntawm US FDA thiab tau txais BTD los ntawm Tuam Tshoj NMPA.
IBI343 tau ua pov thawj tias muaj kev txhawb nqa rau kev teb rau qog nqaij hlav thiab kev ciaj sia nyob zoo
Txoj kev tshawb fawb no tau tshuaj xyuas cov ntaub ntawv ua tau zoo ntawm cov neeg mob uas muaj kev qhia tawm siab ntawm CLDN18.2 (≥75% cov qog nqaij hlav nrog cov xim pleev xim membranous ≥2+ los ntawm IHC), hauv ob pawg koob tshuaj ntawm 6 mg / kg thiab 8 mg / kg.
Ntawm 6 mg/kg (N=31), 15 tus neeg mob muaj cov lus teb tsis txaus (PR) suav nrog 9 tus neeg mob uas tau lees paub PRs thiab 1 tus neeg mob tos kev lees paub. Qhov ORR uas tau lees paub yog 29.0% (95% CI: 14.2-48.0) thiab tus nqi tswj kab mob (DCR) yog 90.3% (95% CI: 74.2-98.0). Hauv 9 tus neeg mob uas tau lees paub cov lus teb, lub sijhawm nruab nrab ntawm kev teb (DoR) yog 5.6 lub hlis (95% CI: 2.8-7.0). Qhov kev saib xyuas nruab nrab yog 10.6 lub hlis (95% CI: 9.7-11.5) rau PFS thiab OS. Qhov nruab nrab PFS yog 5.5 lub hlis (95% CI: 4.1-7.0). Cov ntaub ntawv OS tsis tau loj hlob nrog qhov nruab nrab OS tam sim no ntawm 10.8 lub hlis (95% CI: 6.8-NC). Tom qab cov ntaub ntawv raug txiav tawm, cov lus teb ntawm 1 tus neeg mob uas tseem tshuav tau lees paub thaum Lub Xya Hli 26, 2024 thiab qhov ORR uas tau lees paub tau hloov kho mus rau 32.3% (95% CI: 16.7-51.4).
Ntawm 8 mg/kg (N=17), 17 tus neeg mob uas muaj kev qhia tawm siab ntawm CLDN 18.2 tau raug soj ntsuam. Ntawm lawv, 9 tus neeg mob muaj PRs suav nrog 8 tus neeg mob tau lees paub PR. Qhov ORR lees paub 47.1% (95% CI: 23.0-72.2), thiab DCR yog 88.2% (95% CI: 63.6-98.5). Hauv yim tus neeg mob uas tau lees paub cov lus teb, qhov nruab nrab DoR yog 5.7 lub hlis (95% CI: 2.7-NC). Ntawm tag nrho G/GEJ adenocarcinoma cov neeg mob uas muaj CLDN18.2 kev qhia tawm siab kho ntawm 8 mg/kg (N=19, suav nrog 1 tus neeg mob los ntawm kev nce koob tshuaj thiab 18 tus neeg mob los ntawm kev nthuav dav koob tshuaj), qhov nruab nrab saib xyuas yog 8.1 lub hlis (95% CI: 7.6-8.5) rau PFS thiab OS. Tus nqi nruab nrab ntawm kev mob nkeeg (PFS) yog 6.8 lub hlis (95% CI: 2.8-7.5), thiab tus nqi nruab nrab ntawm kev mob nkeeg (OS) tsis tau mus txog nrog cov xwm txheej tshwm sim hauv 36.8% cov neeg mob.
IBI343 kuj tau ua pov thawj tias muaj kev nyab xeeb zoo dua
Ntawm txhua tus neeg mob uas muaj G/GEJ adenocarcinoma (n = 116, suav nrog 8 tus neeg mob uas muaj mob qog noj ntshav hauv plab los ntawm theem nce ntxiv ntawm cov tshuaj), 66.4% cov neeg mob (77/116) muaj ≥3 qib TEAEs. Cov ≥3 qib TEAEs feem ntau (≥35%) yog cov lej neutrophil txo qis (28.4%), cov lej ntshav dawb txo qis (25.9%), thiab ntshav tsis txaus (16.4%). Muaj ob peb qib ≥3 cov xwm txheej tsis zoo ntawm txoj hnyuv plab, suav nrog tsuas yog 1.7% ntawm qib ≥3 xeev siab. Tsis muaj kab mob ntsws interstitial ntawm txhua qib tau tshaj tawm. Kev lom tshuaj lom cuam tshuam nrog kev kho mob tau txo qis nrog kev kho mob txhawb nqa txaus, thiab kev nyab xeeb tag nrho yog qhov ua tau.
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
WeChat ID: 17801183037
Email:myimmnet@163.com
Lub sijhawm tshaj tawm: Lub Xya Hli-22-2025