A Study of GFH375 in Patients With Advanced Solid Tumors With KRAS G12D Mutations

Conditions

Advanced Solid Tumors, KRAS G12D Mutations

Brief summary

This is a multicenter, open-label, phase I/II study to explore the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of GFH375 in patients with advanced solid tumors harboring a KRAS G12D mutation.

Ai X, Song Z, Wu L, Zhou A, Cheng D, Zong H, Wu H, Niu Z, Sun Y, Zhu L, Li Z, Deng Y, Yuan Y, Qu X, Zhao H, Du Y, Li Z, Wang Y, Shen H, Zhu H, Zheng C, Wang S, Cui Z, Tai L, Lu S.

2026-09-15

10.1038/s41591-026-04559-4

Preliminary efficacy of GFH375 in patients with advanced cholangiocarcinoma or colorectal cancer harboring KRAS G12D mutation.

Lingjun Zhu, Yanhong Deng, Hong Zong, Hongyun Zhao, Aiping Zhou et al. (20 authors)

Journal of Clinical Oncology2026-05-27

10.1200/jco.2026.44.16_suppl.3008

Abstract 7100: VS-7375: An oral, selective KRAS G12D dual ON/OFF inhibitor with potent anti-tumor activity as a single agent and in combination with other agents

Silvia Coma, I E Smith, Cristina Caffarra Malvezzi, Clint A. Stalnecker, Emilia Berardelli et al. (11 authors)

Cancer Research2026-04-03

10.1158/1538-7445.am2026-7100

Abstract PR007: Anti-tumor efficacy of the selective oral KRAS G12D dual ON/OFF inhibitor VS-7375 as a single agent and in combination with targeted agents

Silvia Coma, Brandon L. Mouery, Ryan D. Mouery, Clint A. Stalnecker, Fusheng Zhou et al. (8 authors)

Cancer Research2026-03-05

10.1158/1538-7445.rasoncother26-pr007

Abstract A076: VS-7375: An oral, selective KRAS G12D dual ON/OFF inhibitor with superior anti-tumor efficacy relative to ON-only KRAS inhibitors

Sílvia Coma, Cristina Caffarra Malvezzi, Feng Yan, Lili Tang, Yu Wang et al. (8 authors)

Molecular Cancer Therapeutics2025-10-22

10.1158/1535-7163.targ-25-a076

A first-in-human phase I/II study of GFH375, a highly selective and potent oral KRAS G12D inhibitor in patients with KRAS G12D mutant advanced solid tumors.

Xinghao Ai, Aiping Zhou, Lin Wu, Zhengbo Song, Zhi-Hua Li et al. (20 authors)

Journal of Clinical Oncology2025-05-285 citations

10.1200/jco.2025.43.16_suppl.3013

Abstract 4394: GFH375 (VS-7375): An oral, selective KRAS G12D (ON/OFF) inhibitor with potent anti-tumor efficacy as single agent and in combination with other anticancer therapies in preclinical models

Jonathan A. Pachter, Feng Yan, Sílvia Coma, Cristina Caffarra Malvezzi, Xiuting Liu et al. (14 authors)

Cancer Research2025-04-213 citations

10.1158/1538-7445.am2025-4394

Interventions

DRUGGFH375

GFH375 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

No

Inclusion criteria

1. Subjects must voluntarily agree to participate in the trial and sign a written informed consent form. 2. Male or female ≥ 18 years old and ≤75 years old. 3. ECOG performance status of 0-1. 4. With a life expectancy of ≥12 weeks. 5. With histologically or cytologically confirmed advanced or metastatic solid tumors harboring KRAS G12D mutation. 6. Have at least one measurable lesion according to RECIST1.1, and the phase Ia allows no measurable lesion. 7. Adequate laboratory parameters during the screening period.

Exclusion criteria

1. Active brain metastases. 2. Prior treatment with a KRAS G12D inhibitor. 3. Palliative radiotherapy was completed within 14 days before the first dose. 4. Have poorly controlled or severe cardiovascular disease. 5. Subjects with active hepatitis B or active hepatitis C. 6. Known allergy to the study drug or its components. 7. Pregnant or lactating women.

Design outcomes

Primary

Measure	Time frame	Description
Phase Ia:The incidence and severity of AEs and SAEs	24 months	The incidence and severity of AEs and SAEs
Phase Ia:The incidence of DLT events	21 days	The incidence of DLT events
Phase Ib:The incidence and severity of AEs and SAEs	24 months	The incidence and severity of AEs and SAEs
Phase II:Overall response rate (ORR)	24 months	For NSCLC cohort： Assessed by BICR according to RECIST 1.1；For other cohorts： Assessed by investigators according to RECIST 1.1；

Secondary

Measure	Time frame	Description
Plasma concentrations	up to 21 days	Plasma concentrations and PK parameters of GFH375
Efficacy endpoints	24 months	Duration of response (DoR)

Countries

China

Contacts

Primary ContactYolanda Zeng

yaozeng@genfleet.com+86 21 6882 1388

Outcome results

None listed