Ngomhla we-15 ku-Epreli, ngo-2025, i-InnoCare Pharma yabhengeza ukuba iZiko loVavanyo lwaMayeza (i-CDE) le-China National Medical Products Administration (i-NMPA) lamkele isicelo esitsha seyeza (i-NDA) kwisizukulwana sayo esitsha se-pan-TRK inhibitor zurletrectinib (ICP-723) sokunyanga izigulane zabantu abadala nabakwishumi elivisayo (ezineminyaka eli-12 ukuya kweli-18 ubudala) ezineethumba eziqinileyo ezigcina i-NTRK gene fusions.
Iijini ze-NTRK fusion zenzeka kwiintlobo ezahlukeneyo zeethumba zabantu abadala kunye nabantwana. Kwezinye iithumba ezingaqhelekanga, ezifana ne-salivary gland carcinoma, umhlaza webele ofihlakeleyo, kunye ne-infantile fibrosarcoma, ukwenzeka kwe-NTRK gene fusion kudlula i-90%[1]. Kuqikelelwa ukuba kukho malunga ne-6,500 iimeko ezintsha zeethumba eziqinileyo ze-NTRK fusion-positive ezifunyaniswayo, eTshayina minyaka le. Kukho iimfuno zeklinikhi ezingafikelelwanga kakhulu kule ndawo ngenxa yokunqongophala kweendlela zonyango ezisebenzayo.
I-Zurletrectinib yi-TRK inhibitor entsha esandul’ ukuphuhliswa ebonakalise ukusebenza ngokuchasene ne-TRK WT kunye ne-mutant kinases.
IBritish Journal of Cancer, eyinxalenye yejenali yesayensi ephambili iNature, ipapashe iphepha elinesihloko esithi “I-Zurletrectinib sisithinteli se-TRK sesizukulwana esilandelayo esinomsebenzi onamandla ngaphakathi kwentloko ngokuchasene nezimila ze-NTRK ezidityanisiweyo kunye nokumelana okujoliswe kuko kwiiarhente zesizukulwana sokuqala”. Le jenali igqibe kwelokuba i-zurletrectinib sisithinteli se-TRK sesizukulwana esilandelayo, esinamandla kakhulu esinokungena okuphezulu ebuchosheni emzimbeni kunye nomsebenzi onamandla ngaphakathi kwentloko kunezinye iiarhente zesizukulwana esilandelayo.
Eli phepha libonise ukuba i-zurletrectinib ibonakalise amandla aqinileyo ngokuchasene ne-TRKA, TRKB, kunye ne-TRKC WT kinases, kunye nokuguqulwa kwe-TRKA G595R kunye ne-TRKA G667C. I-Zurletrectinib yayisebenza ngakumbi kunezinye izizukulwana zokuqala ezivunyiweyo yi-FDA okanye ezivavanyiweyo ngokwezonyango (i-larotrectinib) kunye nezizukulwana ezilandelayo (selitrectinib kunye ne-repotrectinib) TRK inhibitors ngokuchasene noninzi lwe-TRK inhibitors resistance mutations. Ngokufanayo, i-zurletrectinib (1 mg/kg BID) yathintela ukukhula kwethumba kwiimodeli ze-xenograft ezivela kwiiseli ze-NTRK fusion-positive kwidosi ephantsi ngokuphindwe ka-30 xa kuthelekiswa ne-selitrectinib.
Eli phepha libonise ngakumbi ukuba, kwisifundo se-CNS penetrant pharmacokinetic kwiimpuku ze-SD, i-zurletrectinib ibonakalise amandla aphuculweyo okungena kumqobo wegazi-ingqondo, ifikelela kwingqondo ngempumelelo ngakumbi kune-selitrectinib kunye ne-repotrectinib. Ukwanda kokungena kwengqondo kweZurletrectinib kuguqulelwe kumsebenzi ophuculweyo wokulwa nomhlaza. Kwimodeli ye-glioma xenograft yegundane le-orthotopic ephethe i-TRKA G598R/G670A resistance mutation, i-zurletrectinib (15 mg/kg) iphucule kakhulu ukusinda kweempuku ezine-orthotopic NTRK fusion-positive, TRK-mutant gliomas (ukusinda okuphakathi = 41.5, 66.5, kunye neentsuku ezili-104 ze-selitrectinib, repotrectinib, kunye ne-zurletrectinib ngokwahlukeneyo; P < 0.05), ebonisa ukusebenza kakuhle xa kuthelekiswa ne-repotrectinib (15 mg/kg) kunye ne-selitrectinib (30 mg/kg) (P=0.0384 kunye ne-0.0022, ngokwahlukeneyo), kunye neprofayili yokhuseleko egqwesileyo.
Okwangoku, kusekho iimvavanyo ezininzi zeklinikhi zobuchwepheshe obutsha bokulwa nomhlaza eTshayina obufuna izigulane. Iingcebiso ngamayeza amatsha kunye nobuchwepheshe, ungaqhagamshelana neSebe leMicimbi yeZibhedlele ze-Oncology zaseBeijing South Region.
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Ixesha leposi: Epreli-17-2025