Hāʻawi ʻo FDA i ka ʻae ʻana o IND no GFH375/VS-7375, kahi mea pale KRAS G12D (ON/OFF) waha, e hiki ai i kahi hoʻāʻo Phase I/IIa e mālama ana i nā ʻōpū paʻa holomua KRAS G12D-mutant ma ʻAmelika Hui Pū ʻIa.

Ma ʻApelila 24, 2025, ua hoʻolaha ʻo GenFleet Therapeutics ua ʻae ʻo US Food and Drug Administration (FDA) i ka noi lāʻau lapaʻau hou (IND) o GFH375/VS-7375, he mea hoʻopaʻa waha KRAS G12D (ON/OFF), no ka hoʻokolohua lapaʻau e mālama ana i nā maʻi puʻupuʻu paʻa holomua me ka hoʻololi ʻana o KRAS G12D. Ua hoʻolālā ʻia ke aʻo ʻana e hoʻomaka ʻia e ka hoa o GenFleet ʻo Verastem Oncology ma US ma kahi o waena o 2025. Ua holomua ke aʻo mua ʻana o GFH375 i hoʻomaka ʻia e GenFleet ma Kina i ka pae II a ua koho ʻia nā ʻikepili pono a me ka palekana mua o kēia aʻo ʻana i loko o ka hōʻike waha wikiwiki ma ka 2025 American Society of Clinical Oncology (ASCO) Annual Meeting e hiki mai ana.

ʻO nā protein RAS, ma ke ʻano GTP-bound a i ʻole GDP-bound hana ʻole, he mau kuapo molekala binary e kāohi ana i nā pane cellular i nā ala hōʻailona e like me RAS-RAF-MEK-ERK a me PI3K/AKT/mTOR. ʻEkolu mau genes RAS e hoʻopili no nā isoforms protein, ʻo ia hoʻi ʻo Kirsten Ras (KRAS), Harvey Ras (HRAS) a me Neuroblastoma Ras (NRAS), a ʻo KRAS ka oncogene i hoʻololi pinepine ʻia i loko o ke kanaka. Ma waena o nā hoʻololi KRAS, ʻo G12D, G12V, a me G12C ke hōʻike nei i nā alleles ʻekolu i hoʻololi pinepine ʻia. Loaʻa pinepine ka hoʻololi KRAS G12D i ka adenocarcinoma ductal pancreatic, ka maʻi ʻaʻai colorectal, a me ka adenocarcinoma māmā.

ʻIke ʻia kahi pakeneka nui o nā maʻi e hūnā ana i ka hoʻololi ʻana o KRAS G12D me ka ʻole o ka mōʻaukala puhipaka a me ka pane maikaʻi ʻole i nā mea hoʻopaʻa PD-1. Hoʻohiki nā mea hoʻopaʻa G12D koho mutant e pōmaikaʻi i nā ʻāpana nui o nā maʻi PDAC i hoʻokele ʻia e KRAS ʻoiai ʻo nā hoʻololi KRAS G12D ka loli somatic pinepine i nā maʻi PDAC (ma kahi o 40%) i hōʻike ʻia he 5 mau makahiki ka nui o ke ola ma lalo o 10%.

He mea hoʻopaʻa waha ʻo GFH375, ikaika, koho nui i nā molekole liʻiliʻi KRAS G12D (ON/OFF) i hoʻolālā ʻia e kuhikuhi i ka hoʻololi GTP/GDP, no laila e hoʻopilikia ana i ka hoʻoulu ʻana o nā ala ma lalo a pale pono i ka hoʻonui ʻana o nā cell tumor. Ua hōʻike nā haʻawina preclinical i ka pale ʻana o ka dose-dependent i nā hiʻohiʻona e lawe ana i ka mutation KRAS G12D; Ua hōʻike pū ʻo GFH375 i ka pilikia haʻahaʻa ma waho o ka pahuhopu i ka kinase selectivity a me nā hoʻāʻo palekana.

I kēia manawa, nui nā hoʻokolohua lapaʻau o nā ʻenehana anti-cancer hou ma Kina e ʻimi nei i nā maʻi. I ke kūkākūkā ʻana i nā lāʻau lapaʻau a me nā ʻenehana hou, hiki iā ʻoe ke hoʻokaʻaʻike aku i ka Beijing South Region Oncology Hospital International Department.

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