Trotabresib is an investigational, oral cancer therapy belonging to a class of drugs known as BET inhibitors. These drugs are designed to interfere with specific processes inside cancer cells to stop the growth of various tumors. Trotabresib’s development focuses on the underlying genetic machinery that fuels difficult-to-treat cancers.
The Role of BET Inhibition in Cancer
A family of proteins called bromodomain and extraterminal (BET) proteins act like bookmarks on our DNA, helping to turn specific genes on. They read epigenetic signals that control which genes are active in a cell. This process is a normal part of cellular function.
In some cancers, this system is hijacked and BET proteins mistakenly activate oncogenes, which are genes that drive tumor development. An example is the MYC gene, which, when overactivated, contributes to the rapid proliferation of cancer cells. This creates a dependency where the cancer relies on BET proteins to sustain its aggressive behavior.
Trotabresib intervenes by binding to BET proteins, which blocks them from reading the DNA instructions that turn on oncogenes. By preventing access to these cancer-driving genes, trotabresib can halt the proliferation of tumor cells.
Cancers Investigated with Trotabresib
Research into trotabresib has focused on cancers with a strong dependence on BET protein activity. One primary target is NUT midline carcinoma, a rare and aggressive cancer defined by a genetic rearrangement involving the NUT gene.
The drug has also been investigated in blood cancers like acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL). For patients with relapsed or refractory DLBCL, trotabresib is explored as a therapeutic option, particularly for those whose disease is associated with MYC gene rearrangements.
Trotabresib has also been studied in a range of advanced solid tumors. Clinical trials have included patients with various tumor types, such as endometrial cancer and thymoma, to assess the drug’s activity and identify other cancers that may be susceptible to BET inhibition.
Current Research and Clinical Trials
Trotabresib is an investigational drug available only through clinical trials. Phase I trials were designed to determine the appropriate dosage, assess safety, and observe preliminary effectiveness. These studies identified a recommended dose and schedule for investigation in larger patient groups.
Trotabresib has shown anti-tumor activity when used as a single agent. In a study of patients with relapsed or refractory diffuse large B-cell lymphoma, an objective response rate of 13% was observed. For patients with advanced solid tumors, a clinical benefit rate of nearly 32% was achieved, meaning a subset of patients experienced disease stabilization.
Research has shown that trotabresib can produce durable responses in some heavily pretreated patients, with a few remaining on treatment for over two years. The drug’s longer half-life has made it a candidate for treating central nervous system tumors like glioblastoma. Future studies aim to explore trotabresib in combination with other anticancer agents.
Known Side Effects
Treatment with trotabresib is associated with side effects that were monitored during clinical trials. The most frequently observed adverse events are manageable and include:
- Fatigue
- Nausea
- Diarrhea
- A decrease in appetite
A more specific category of side effects involves hematological toxicities, which are effects on the blood and bone marrow. One of the most common severe events is thrombocytopenia, a low count of platelets needed for clotting. Another is anemia, a deficiency of red blood cells that can cause fatigue.
These hematological issues are a known effect of BET inhibitors and require close monitoring during treatment. Managing these side effects is a primary focus in clinical trials to ensure patient safety and allow individuals to continue treatment as long as it is beneficial.