Datopotamab deruxtecan is an investigational cancer treatment designed to precisely target cancer cells. It falls under a class of drugs known as antibody-drug conjugates (ADCs), representing a sophisticated approach in modern oncology. This therapy aims to deliver potent agents directly to malignant cells, differentiating it from traditional chemotherapy that can affect healthy tissues.
How Datopotamab Deruxtecan Works
Datopotamab deruxtecan combines the specificity of an antibody with the cell-killing power of a chemotherapy drug. It consists of three main parts: an antibody, a linker, and a cytotoxic payload called deruxtecan. The antibody specifically targets TROP2, a protein frequently found on the surface of various cancer cells, including those in breast cancer.
Once the antibody binds to TROP2, the ADC is internalized into the cell through endocytosis. Inside the cancer cell, the linker is cleaved by enzymes, releasing deruxtecan directly into the cancerous environment. This targeted delivery helps to minimize damage to healthy cells. The released deruxtecan then interferes with DNA replication, leading to cell cycle arrest and ultimately cell death.
Specific Breast Cancer Applications
Datopotamab deruxtecan is being investigated for its potential in specific subtypes of breast cancer, particularly hormone receptor-positive/HER2-negative (HR+/HER2-) and triple-negative breast cancer (TNBC). TROP2, the protein targeted by datopotamab deruxtecan, is broadly expressed in these breast cancer subtypes and is associated with a poorer prognosis. This makes TROP2 an attractive target for delivering anti-cancer agents directly to these tumor cells. For patients with advanced or metastatic HR+/HER2- breast cancer and TNBC, treatment options can be limited after progression on standard therapies, making new targeted approaches important. The ongoing TROPION-Breast01 and TROPION-Breast02 trials are specifically evaluating this drug in these patient populations.
Clinical Trial Outcomes
Clinical trials, such as TROPION-PanTumor01 and TROPION-Breast01, have investigated the efficacy and safety of datopotamab deruxtecan in breast cancer. In the phase I TROPION-PanTumor01 study, which included patients with heavily pretreated HR+/HER2- breast cancer and TNBC, clinical activity and a manageable safety profile were observed. Objective response rate (ORR), which measures the percentage of patients whose tumors shrink or disappear, was 26.8% for HR+/HER2- breast cancer and 31.8% for TNBC patients. Progression-free survival (PFS), the length of time a patient lives with the disease without it getting worse, was 8.3 months for HR+/HER2- breast cancer and 4.4 months for TNBC in this study. The median duration of response was not evaluable for HR+/HER2- breast cancer but was 16.8 months for TNBC.
The TROPION-Breast01 Phase III trial, comparing datopotamab deruxtecan to standard chemotherapy in HR-positive, HER2-low or negative breast cancer, met its primary endpoint of progression-free survival, showing a statistically significant and clinically meaningful improvement. However, the final analysis for overall survival (OS) in TROPION-Breast01 did not achieve statistical significance compared to chemotherapy.
Common side effects observed in clinical trials include stomatitis (mouth sores), nausea, fatigue, and alopecia (hair loss). Stomatitis was a frequently reported treatment-emergent adverse event, mostly mild to moderate in severity. Interstitial lung disease (ILD) is a known adverse event associated with deruxtecan-based ADCs and is carefully monitored in ongoing studies. While rates of ILD have remained low, some cases, including severe ones, have been reported. Prophylactic measures and prompt management, including corticosteroid treatment, are implemented to mitigate these adverse events.
Patient Experience and Administration
Datopotamab deruxtecan is typically administered as an intravenous (IV) infusion on day 1 of each 21-day cycle, meaning once every three weeks. Patients can expect to receive the infusion in a healthcare setting, similar to other intravenous chemotherapy or targeted therapies. The duration of each infusion session may vary, and patients are usually monitored for any immediate reactions during and after administration.
During treatment, patients are carefully monitored for potential specific adverse events, including stomatitis, ocular surface events, and interstitial lung disease. Prophylaxis for certain side effects, such as antiemetic medication for nausea and steroid mouthwash for stomatitis, may be implemented.