Kev Sib xyaw Ntawm Cov Khib / Eisai Keytruda + Lenvima Hauv Kev Kho Mob 7 Ntau Hom Mob Txawv Tawv Qhia Tau Qhia Nws Qhov Ua Tau Zoo

Merck& Co thiab nws tus khub Eisai tsis ntev los no tshaj tawm cov ntaub ntawv tshiab los ntawm ob qhov kev sim ntawm LEAP (LEnvatinib Thiab Pembrolizumab) cov haujlwm hauv chaw ua haujlwm ntawm 2020 European Society of Medical Oncology (ESMO) lub rooj sib tham virtual. Ob qhov kev sim no yog soj ntsuam Merck's anti-PD-1 txoj kev kho mob Keytruda (pembrolizumab) nrog Eisai lub qhov ncauj ntau tus kabmob tyrosine kinase inhibitor Lenvima (lenvatinib) rau kev kho mob ntawm ntau hom mob qog nqaij hlav.

Cov txiaj ntsig pom tau hais tias Keytruda + Lenvima kev sib xyaw ua ke tau qhia txog kev ua tau zoo hauv 7 hom qog: (1) Hauv Kev Ua 2 Theem-LEAP-004 kev sim, qhov kev kho mob sib xyaw ua ntej tau txais kev kho los tiv thaiv PD-1 / PD-L1 rau qhov tsis muaj kev tiv thaiv lossis Lub hom phiaj tau teb (ORR) ntawm cov neeg mob uas ua paug metanatic yog 21.4%. (2) Hauv Kev Ua Rau Theem 2 LEAP-005 sim, muaj mob cancer mis triple-negative (TNBC), mob kheesxaws ntawm zes qe menyuam, mob plab hnyuv, mob plab hnyuv (siab tsis yog-microsatellite instability [tsis-MSI-H] / tsis ncaj ncees lawm Cov neeg mob uas tau kho kom zoo pMMR]), glioblastoma multiforme (GBM), thiab cholangiocarcinoma (BTC), ORR ntawm Keytruda + Lenvima kev sib xyaw ua ke yog 9.7-32.3% (95% CI: 2.0-51.4%).

Txog tam sim no, Keytruda + Lenvima kev sib xyaw ua ke tau kawm hauv 13 ntau hom qog thiab tau qhia tias muaj kev ua tau zoo hauv ntau hom qog. Thawj cov ntaub ntawv los ntawm ob qhov kev sim kho mob ntawm qhov haujlwm LEAP tshaj tawm hauv lub rooj sib tham no txhawb ntxiv cov kev kho mob muaj peev xwm ntawm kev sib xyaw.

——Phase 2 LEAP-004 kev sim (NCT03776136): ua rau cov neeg mob uas tsis tuaj yeem tiv thaiv lossis muaj tus mob melanoma uas yav tas los tau txais kev tiv thaiv PD-1 / PD-L1 kho rau kev kho tsis tuaj yeem lossis nce siab melanoma uas tau nce hauv 12 lub lis piam, raws li Lub Rau Hli 10, 2020 Muaj tag nrho ntawm 103 tus neeg mob tau sau npe thiab kho nyob rau tib hnub.

Cov ntaub ntawv qhia tau hais tias: kev soj ntsuam nruab nrab ntawm 12 lub hlis, lub ntsiab lus teb (ORR) ntawm Keytruda {{2}} Lenvima kev sib xyaw ua ke yog 21.4% (95% CI: 13.9-30.5), tus nqi teb tag (CR) ) yog 1.9% (n = 2), Feem ntawm cov feem lus teb (PR) yog 19.4% (n = 20). Hauv tag nrho cov tib neeg kawm, qhov nruab nrab ntawm kev teb (DOR) yog 6.3 lub hlis (thaj tsam: 2.1+ txog 11.1+), thiab 72.6% (95% CI: 46.2-87.6) cov lus teb tau nce mus txog ≥6 lub hlis. Qhov nruab nrab ntawm PFS tau li ntawm 4.2 lub hlis (thaj tsam: 3.5-6.3), 73.8% ntawm cov neeg mob tau muaj tus mob lossis tuag taus, thiab 9-lub hlis PFS yog 26.2% (95% CI: 17.4-35.9). Qhov nruab nrab tag nrho cov muaj sia nyob (OS) yog 13.9 lub hlis (thaj tsam: 10.8-tsis mus txog), thiab 44.7% ntawm cov neeg mob tuag. Lub 9 hli OS cov nqi yog 65.4% (95% CI: 55.2-73.8).

Kev tshawb nrhiav pom tau hais tias ntawm 29 tus neeg mob uas yav tas los tau txais kev kho mob los ntawm kev tiv thaiv PD-1 / L1 thiab kev tiv thaiv CTLA-4, ORR yog 31.0% (95% CI: 15.3-50.8) thiab CR yog 3.4. % (N=1), PR yog 27.6% (n=8), thiab tus nqi tswj kab mob (DCR) yog 62.1% (95% CI: 55.0-74.2).

Kev kho mob ntsig txog qhov tshwm sim tsis zoo (TRAE) ua rau 7.8% ntawm cov neeg mob tsis kho Keytruda thiab / lossis Lenvima kho mob. Tsawg kawg 30% ntawm cov neeg kawm, feem ntau TRAEs ntawm ib qib yog kub siab (56.3%), raws plab (35.9%), xeev siab (34.0%), hypothyroidism (33.0%), thiab tsis qab los noj mov (31.1%) Cov.

——Phase 2 LEAP-005 mus sib hais (NCT03797326): Tshuaj xyuas qhov ua tau zoo thiab kev nyab xeeb ntawm Keytruda + Lenvima sib xyaw ua ke hauv cov neeg mob uas muaj ntau cov qog ua haujlwm dhau los uas tau txais kev kho mob. Cov pawg sib koom ua ke muaj xws li: TNBC, mob kheesxaws ntawm zes qe menyuam, mob plab, mob plab hnyuv plab hnyuv plab hnyuv plab hnyuv plab hnyuv plab hnyuv hnyuv, (tsis-MSI-H / pMMR), GBM, BTC. Txog Lub Plaub Hlis 10, 2020, tag nrho muaj 187 tus neeg mob tau sau npe thiab kho mob. Cov sijhawm nruab nrab rov qab los ntawm 6 hom mob qog cov neeg mob yog 8.6 lub hlis (thaj tsam: 1.9-13.1). Qhov ua tau zoo yog raws li nram no.

Tsawg kawg 20% ​​ntawm cov neeg kawm, feem ntau TAS ntawm ib qib yog kub siab (39.0%), qaug zog (29.4%), mob plab zom mov (26.7%), tsis qab los noj mov (25.1%), hypothyroidism (27.8%), thiab xeev siab (21.9%). Qhov kev tshawb fawb no tseem muaj thiab yuav nthuav dav rau kwv yees li 100 tus neeg mob hauv ib pawg neeg sib koom tes.

Keytruda + Lenvima kev sib xyaw ua ke yog ib feem ntawm txoj kev sib koom tes ua ke ntawm Merck thiab Eisai Oncology. Thaum Lub Peb Hlis 2018, ob tog tau kos npe rau kev koom tes sib koom ua lag luam tag nrho US $ 5.8 billion los tsim ib cov tshuaj ntawm Lenvima thiab kev sib xyaw nrog Keytruda rau kev kho mob ntawm ntau hom qog.

Lenvima yog qhov ncauj ntau-receptor tyrosine kinase (RTK) inhibitor nrog hom tshiab khi hom. Ntxiv rau kev tiv thaiv lwm yam pro-angiogenic thiab oncogenic teeb liab txog kev mob ntsig txog qog angiogenesis, kev mob qog thiab cov qog ua haujlwm hloov kho, RTK (suav nrog ntxiv rau platelet-derived growth factor (PDGF) receptors PDGFRα, KIT thiab RET), nws kuj tseem tuaj yeem xaiv inhibit vascular endothelial kev loj hlob yam (VEGF) receptors (VEGFR1, VEGFR2, VEGFR3) thiab fibroblast kev loj hlob tau (FGF) receptors (FGFR1, FGFR2, FGFR3, FGFR4) kinase kev ua si.

Keytruda yog qhov los tiv thaiv PD-1 qog tshuaj tiv thaiv kab mob uas pab tshawb nrhiav thiab tua cov qog hlwb los ntawm kev txhim kho kev muaj peev xwm ntawm tib neeg lub cev tsis muaj zog. Keytruda yog tib neeg cov monoclonal antibody uas cuam tshuam kev cuam tshuam ntawm PD-1 thiab nws cov ligands PD-L1 thiab PD-L2, yog li ua kom T lymphocytes uas yuav cuam tshuam cov qog hlwb thiab cov hlwb noj qab haus huv.