Oral KRAS G12D inhibitor GFH375 for previously treated advanced solid tumors with KRASG12D mutations: a phase 1 trial.

doi:10.1038/s41591-026-04559-4

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Article

Oral KRAS G12D inhibitor GFH375 for previously treated advanced solid tumors with KRASG12D mutations: a phase 1 trial.

Nature medicine - 1 Sept 2026

Ai Xinghao, Song Zhengbo, Wu Lin, Zhou Aiping, Cheng Di, Zong Hong, Wu Heshui, Niu Zuoxing, Sun Yuping, Zhu Lingjun, Li Zhiwei, Deng Yanhong, Yuan Ying, Qu Xiujuan, Zhao Haitao, Du Yingying, Li Ziming, Wang Yu, Shen Haige, Zhu Huaqiang, Zheng Chanli, Wang Shuang, Cui Zhao, Tai Lingyu, Lu Shun

Abstract excerpt

Kirsten rat sarcoma viral oncogene homolog (KRAS)G12D is the most prevalent RAS mutation in solid tumors, associated with poor prognosis, and occurs mainly in pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). Here we evaluated GFH375, a compound that targets both 'ON' (GTP-bound) and 'OFF' (GDP-bound) states of KRASG12D proteins, in a phase 1 dose-escalation...

Read the complete abstract on PubMed

Topics

Humans
Female
Male
Proto-Oncogene Proteins p21(ras)
Aged

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Middle Aged

Mutation

Adult

Administration, Oral

Carcinoma, Non-Small-Cell Lung

Aged, 80 and over

Neoplasms

Maximum Tolerated Dose

Carcinoma, Pancreatic Ductal

Colorectal Neoplasms

Lung Neoplasms

Source

Open in PubMed

Identifiers

PMID: 42745055
DOI: 10.1038/s41591-026-04559-4

Genes

KRAS

Variants

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 25 Oct 2026.

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