Trodelvy™ (sacituzumab govitecan-hziy)
Trodelvy (sacituzumab govitecan-hziy) is the first and the only approved antibody-drug conjugate for the treatment of advanced triple-negative breast cancer (TNBC) in adult patients.
Patients who received at least two therapies for the metastatic disease earlier are eligible for the treatment.
The drug was developed by Immunomedics, which submitted a biologics license application (BLA) for the drug to the US Food and Drug Administration (FDA) in May 2018. The application was rejected due to several developmental and chemical concerns.
Immunomedics collaborated with Everest Medicines for the development, registration and commercialisation of sacituzumab govitecan in Greater China, South Korea and some Southeast Asian territories in April 2019.
The company resubmitted the BLA after addressing the concerns for accelerated approval in December 2019.
Trodelvy received fast track designation for the treatment of advanced or locally metastatic urothelial cancer in April 2020. It received accelerated approval from the FDA to treat advanced TNBC in adult patients in the same month. The drug also holds breakthrough therapy status.
Trodelvy is available as an injection for intravenous administration in a single-dose vial of 180mg off-white to yellow coloured lyophilised powder.
TNBC is an aggressive form of cancer, which accounts for approximately 20% of all the types of breast cancers.
Patients with TNBC do not have any receptors, typically estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2), generally expressed in the breast cancers. The lack of receptors makes the disease difficult to treat.
The disease affects both men and women equally and patients are prone to relapse within the first three years of treatment. People belonging to African-American or Latin origin, women under 40 and those with BRCA gene mutation are more likely to be at risk of TNBC.
The most common symptoms of the disease are a lump in the breast, breast pain or redness and change in nipple structure with certain discharge.
Trodelvy is a Trop-2-directed antibody and topoisomerase inhibitor conjugate drug.
It targets the Trop-2 antigen, a humanised monoclonal antibody, expressed on various tumour cells and delivers SN-38, a topoisomerase I inhibitor, to the tumours directly, causing cell death.
The hydrolysable linker, CL2A connects the Trop-2-directed antibody to the cytotoxic drug SN-38.
Trodelvy is currently being studied to address approximately eight difficult-to-treat solid cancers.
FDA approval of Trodelvy was based on a multicentre, single-arm, phase two clinical trial, IMMU-132-01; 108 patients with metastatic TNBC were enrolled to study the efficacy of the drug. The primary goals of the trial were tumour response rate and duration of response.
In a 21-day treatment cycle, the patients received 10mg/kg of Trodelvy on days 1 and 8. Tumour imaging was performed at every eight weeks with CT or MRI scans for four to six weeks after a partial or complete response. Treatment was continued until disease progression or development of intolerance to the therapy.
Patients demonstrated the overall response rate of 33% in the trial, of which 30.6% of patients showed partial response and 2.8% of patients showed a complete response, while the median duration of response of 7.7 months was observed in the patients.
A phase three confirmatory trial, ASCENT being performed in more than 500 patients will be halted early due to convincingly powerful efficacy results across multiple parameters. Top-line results from the study will be achieved by mid-2020. The study validated the safety and efficacy data of the drug observed in phase two clinical study.
The most common adverse events observed in the patients during the IMMU-132-01 clinical trial were diarrhoea, fatigue, nausea, vomiting, baldness, constipation, rashes on the skin, abdominal pain, neutropenia and loss of appetite.
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