Clinical Trials | A Phase 2, Open Label, Multicenter, Randomized Study, to Evaluate the Efficacy and Safety of Denikitug Monotherapy and Denikitug-based Combinations in Participants With Advanced Microsatellite Stable (MSS) Colorectal Cancer (CRC)

The UVA Comprehensive Cancer Center seeks adults ages 18 and over with Advanced Microsatellite Stable (MSS) Colorectal Cancer (CRC) that have previously received up to 2 prior lines of therapy with 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab +/- other targeted therapies. The purpose of this study is to learn if the investigational drug denikitug (DEN) can help to control advanced CRC. They want to test DEN by itself and combined with the cancer drugs nivolumab (NIVO), trifluridine-tipiracil (FTD-TPI), and/or bevacizumab (BVZ). DEN and the combination of DEN with NIVO, FTD-TPI, and/or BVZ are considered investigational because they have not been approved by the United States Food and Drug Administration (FDA). DEN is not approved by any health authority, such as the FDA. It is an investigational drug, so it is only being used in research. NIVO, FTD-TPI, and BVZ are currently approved by the FDA for use in other types of cancer. However, they are not approved by the FDA to be given in combination with DEN. If you participate in the study, the study drug(s) you get will depend on when you join the study. If you are one of the first about 10 participants in the study, you will get DEN, FTD-TPI, and BVZ. This is called the safety run-in. This step is done to evaluate whether the dose level of DEN in combination with FTD-TPI and BVZ is well tolerated and safe for participants in this study. If you join the study after the safety run-in period, we will randomly assign you to DEN or a study drug combination. That means the study drug(s) you get are chosen by chance. We will use a computer to randomly assign you to one of the following study drug combinations: Group A: DEN Group B: DEN and NIVO Group C: DEN, FTD-TPI, and BVZ Group D: FTD-TPI and BVZ If you are in this part of the study, you will have an equal chance (25%) of being in each group. You will know which group you are in. How long you get the study drug(s) will depend on which study drug you get and how your body responds to the study drug(s). If you get DEN, you may get it for up to about 2 years. If you get NIVO, you may get it until you stop taking DEN. If you get FTD-TPI and BVZ, you may get them for as long as you are tolerating and appropriately responding to them. 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, dosing 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 dosing period. During the dosing 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. After you stop the study drug(s) for any reason, you will have an end-of-dosing visit within or about 1 month after your last dose of study drug(s). For the follow-up period, you will have safety follow-up visits about every month for 4 months after your last dose of study drugs or until you start a new anticancer treatment. The 1-month, 3-month, and 4-month safety follow-up visits will happen in the clinic. The 2-month safety follow-up visit may be done by phone. The investigational drugs, Denikitug (GS-1811) and Nivolumab (NIVO), will be provided by the sponsor at no cost to you. You or your insurance may need to pay for Trifluridine-Tipiracil (FTD-TPI) and Bevacizumab (BVZ), which are considered the current standard of care. They will not cost more than what you would pay if you were not in the study. 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/NCT07527858 [email protected]