Clinical Trials | A Phase 2, Open-label Study of VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, with and without an anti-EGFR antibody, and with an anti-EGFR antibody and Chemotherapy in Patients with Metastatic KRAS G12D-Mutated Colorectal Adenocarcinoma (TARGET-D 203)

The UVA Comprehensive Cancer Center seeks adults ages 18 and over with Metastatic KRAS G12D-Mutated Colorectal Adenocarcinoma. If you choose to participate in this study, you will receive an investigational new drug, VS-7375. “Investigational new drug” means a drug that has not been approved by the FDA to be prescribed or sold. The main aims of this clinical study are to: • Find out if VS-7375 alone or in combination with cetuximab or panitumumab is better at prolonging the time it takes for disease progression. • Understand the side effects and risks of VS-7375 alone and in combination with cetuximab or panitumumab. • Learn how well and how long VS-7375 alone or given with cetuximab or panitumumab may work to treat cancers with KRAS G12D mutations. • Understand the side effects and risks of VS-7375 in combination with cetuximab and mFOLFOX6. • Learn how well and how long VS-7375 in combination with cetuximab and mFOLFOX6 may work to treat cancers with KRAS G12D mutations. • Measure the amount of VS-7375 in your blood at different times (this is called pharmacokinetics or PK). This study will look at a potential treatment (VS-7375 alone, VS-7375 in combination with cetuximab or panitumumab, or VS-7375 in combination with cetuximab and mFOLFOX6) in patients with metastatic colorectal adenocarcinoma that have a KRAS G12D mutation. The study will be conducted in three main parts: Part A, Part B, and Part C. Your study doctor will tell you which part of the study you qualify for during the screening period so that you will know before starting any study drug. The study involves receiving the investigational drugs, as well as coming in for study visits, which include exams, laboratory tests, and procedures such as having your blood drawn, imaging, and talking to the study doctor. If you choose to participate the study will consist of three parts: a screening period, a treatment period, and follow-up period. The screening period is where the study team will see if you are eligible for the study. After screening, if you are deemed eligible for participation and consent to participate in the study, you will enter the treatment period. During the treatment period, your assigned study drug(s) will be given in 4-week cycles. How you receive the study drug(s) depends on which group you are in. For the follow-up period, the study team will remain in contact with you, either in person at clinic visits or by phone calls to see how you are doing. The investigational drugs (VS-7375 and cetuximab), will be provided by the sponsor at no cost to you. All additional study procedures that are beyond your standard medical care, including laboratory tests, physical examinations, and visits to the study center, are provided to you at no charge. Additional information can be found here: https://clinicaltrials.gov/study/NCT07659795 [email protected]