Sacituzumab tirumotecan represents a modern approach in cancer treatment, belonging to a category of medicines known as antibody-drug conjugates (ADCs). This medication is designed to deliver potent chemotherapy directly to cancer cells. It holds particular relevance for individuals facing specific types of advanced or metastatic cancers. The development of sacituzumab tirumotecan aims to enhance the precision of cancer therapy.
Mechanism of Action
Sacituzumab tirumotecan operates like a targeted delivery system. The first component is a monoclonal antibody, sacituzumab, engineered to specifically recognize and bind to a protein called Trop-2. Trop-2 is frequently found in elevated amounts on the surface of various solid tumor cells.
Once the antibody attaches to the Trop-2 protein on a cancer cell, the entire antibody-drug conjugate is drawn inside the cell. Inside the cancer cell, a unique, stable linker connecting the antibody to the drug payload is designed to break apart. This action releases the chemotherapy agent, known as tirumotecan, which is a topoisomerase I inhibitor with the active form KL610023.
The released chemotherapy drug, KL610023, then interferes with the cancer cell’s ability to repair its DNA. It specifically inhibits topoisomerase I, an enzyme that plays a role in DNA replication. This interference leads to DNA damage, preventing the cancer cell from dividing and ultimately causing its death. Furthermore, the hydrolytically cleavable linker allows for the release of the payload not only inside the targeted cell but also into the surrounding tumor microenvironment, potentially affecting nearby cancer cells, a phenomenon known as the “bystander effect.”
Approved Medical Uses
Sacituzumab tirumotecan is approved for the treatment of specific advanced cancers in certain regions. In China, the National Medical Products Administration (NMPA) has granted marketing authorization for this drug for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). This approval is for those who have already undergone at least two prior systemic therapies, with at least one for the advanced or metastatic stage of the disease.
The NMPA has also approved sacituzumab tirumotecan for adult patients with epidermal growth factor receptor (EGFR) mutant-positive locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). This indication is specifically for patients whose disease has progressed following treatment with an EGFR-tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy.
Administration and Dosing
Sacituzumab tirumotecan is administered to patients as an intravenous (IV) infusion. It has typically been given at a dose of 4 mg/kg of body weight. The treatment usually follows a schedule of every two weeks (Q2W).
Patients commonly receive pre-medications before each infusion. These pre-medications aim to reduce or prevent potential side effects like infusion-related reactions or nausea and vomiting. The infusion duration can vary. Treatment continues until the disease progresses or unacceptable side effects occur.
Potential Side Effects
Patients receiving sacituzumab tirumotecan may experience a range of side effects. Frequently reported adverse reactions include nausea, diarrhea, fatigue, hair loss, anemia, vomiting, constipation, rash, and decreased appetite. Patients may also experience abdominal pain or respiratory infections.
Two significant side effects carry boxed warnings due to their potential severity: severe neutropenia and severe diarrhea. Neutropenia refers to an abnormally low count of neutrophils, a type of white blood cell that helps fight infection. Occurring in about 64% of patients, with severe (Grade 3-4) neutropenia observed in nearly half of treated individuals, this increases the risk of serious infections.
Severe diarrhea is also a common concern, affecting about 64% of patients, with severe (Grade 3-4) cases occurring in approximately 11% of patients. This can lead to dehydration and kidney problems. Patients should be closely monitored for diarrhea, and if it occurs, infectious causes should be ruled out, followed by prompt initiation of anti-diarrhea medication like loperamide.
Other serious effects include hypersensitivity and infusion-related reactions, which can be severe. Patients should communicate any side effects they experience with their healthcare team promptly. Managing these side effects often involves withholding or reducing the drug dose, along with supportive care such as fluid and electrolyte replacement or administration of granulocyte colony-stimulating factors (G-CSF) for neutropenia.