Investigating the Potential of DCC-3009 in Advanced GIST

Following the 2025 Connective Tissue Oncology Society (CTOS) Annual Meeting, Dr. Suzanne George sat down with CURE for an interview to discuss the ongoing phase 1/2 DCC-3009 study in advanced gastrointestinal stromal tumor (GIST). The trial-in-progress presentation highlighted the rationale behind the investigational agent, its study design, and the unmet needs it aims to address for patients whose disease has progressed on multiple prior targeted therapies.

George is a senior physician and chief of the Division of Sarcoma at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, in Boston Massachusetts.

CURE: To kick things off, can you explain to patients the overall goal of the DCC-3009 phase 1/2 study?

George: The phase 1/2 study is evaluating a new compound called DCC-3009. It is a drug that was designed specifically to work well in patients with advanced gastrointestinal stromal tumor, or GIST. The primary goal of the study is to evaluate what the right dose is and what the safety profile of this drug looks like.

The study is a first-in-human study. As would be typical for a first-in-human study, patients are treated in small groups or cohorts at slowly escalating doses in order to identify the ‘right dose’ to move forward into further testing. That is the first goal of the study. The second goal is to determine, as you are evaluating this drug for the first time in people, what the side effect profile looks like.

At the same time, even though those are the primary goals of the study, we always look to see how the drug is working against the disease, as all patients enrolled will have a diagnosis of GIST.

For patients who previously progressed on multiple targeted therapies, what key features of DCC-3009 should they understand, particularly its intended mechanism?

DCC-3009 is what we would call a pan-inhibitor, so it blocks both the primary driver mutations in KIT, and we think it also blocks a wide range of secondary resistance mutations in KIT. In the example that you mentioned, for people who have already been treated for GIST with other drugs, if the disease has subsequently grown despite being treated with those drugs, it's likely that the tumors have developed some form of resistance to those earlier medications.

What we know is that the primary mechanism of resistance to earlier lines of therapy in GIST is developing new mutations, typically in that same driver we call KIT. Therefore, patients with resistant GIST usually have tumors with multiple mutations in this KIT gene, leading to its mutated protein. DCC-3009 is designed to block these resistance mutations in addition to the primary mutations, and it is designed to try to do that better than currently available drugs.

What can you share about study participation in terms of visit frequency, monitoring procedures, and management of side effects?

Because it's an early-phase study, the schedule is rather intensive, especially at the beginning when people are first starting on the study. Patients need to come in for one or two doses even before they start their daily dose in order for the study team to begin to learn about how the drug is metabolized in the body and what the drug levels look like. So, the beginning part of the study is relatively intensive with frequent visits, but over time, the visit schedule does start to spread out to every couple of weeks, and then it will likely spread out even further beyond that.

What's important to know is that even though the study requires these intensive visits initially, they slowly will spread out over time. There may be times where your study team asks you to come in more frequently because it's just the right thing to do for people's clinical care. Because these are new drugs, we want to watch people closely, and we want to make sure that there's adequate support for any side effects that come up. At the same time, we want to make sure that if people aren't having side effects, we know that too.

These early-phase studies really require a lot of interaction with the study team in order to make sure that we really understand how these new drugs are impacting patients.

Can you please share the key findings of the study, and what was shared at the 2025 CTOS Annual Meeting?

The study presented is a trial in progress. For a trial in progress, we typically share the rationale behind the study, what the study involves, and the fact that the study is still open, ongoing, and accruing patients. Therefore, there are no results available yet from the study because it is just too early in its development. But the reason that we presented this study is because we think it is an interesting study that could potentially fill an unmet need in patients with advanced GIST, and we want patients and providers to be aware of this study as a potential option for people who would be interested in participating.

I think the important thing to know about these early studies is that they are often open at a relatively limited number of centers. The reason for that is really because, in these early-phase studies, as I mentioned earlier, we need to make sure that we really understand the side effects, the tolerance, and how the drug is working. Because of that, usually, it is just open at a more contained number of sites.

So, if this is a study that people are interested in participating in, it is just important to get a sense of which sites are open and to connect to the sites that are actively participating.

Transcript has been edited for clarity and conciseness.

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