Sacituzumab Govitecan
Sacituzumab Govitecan Uses, Dosage, Side Effects, Food Interaction and all others data.
Metastatic triple-negative breast cancer (mTNBC) is an aggressive form of breast cancer with limited treatment options involving cytotoxic chemotherapy agents. Targeted chemotherapy through the application of antibody-conjugated agents (ADCs) is a recent advance in cancer treatment. One such ADC is sacituzumab govitecan, which combines a humanized anti-trophoblast cell-surface antigen 2 (TROP-2) antibody with the topoisomerase I inhibitor SN-38.
Sacituzumab Govitecan was granted FDA approval on April 22nd, 2020 and is marketed under the brand name Trodelvy™ by Immunomedics, Inc.; it is currently indicated under accelerated approval for the treatment of mTNBC patients who have undergone two or more prior therapies. As a targeted cytotoxic agent, it is hoped to provide similar efficacy with reduced adverse effects.
Sacituzumab Govitecan is a humanized monoclonal antibody/topoisomerase inhibitor conjugate designed to induce DNA damage-mediated cell death preferentially in TROP-2-expressing cancer cells. Detailed pharmacodynamic studies have not been performed for sacituzumab govitecan, although as a therapeutic protein, there is potential for immunogenicity. In addition, sacituzumab govitecan has the potential to cause severe hypersensitivity, nausea and vomiting, and embryo-fetal toxicity. Patients who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia.
| Trade Name | Sacituzumab Govitecan |
| Generic | Sacituzumab govitecan |
| Sacituzumab govitecan Other Names | Sacituzumab govitecan, sacituzumab govitecan-hziy |
| Weight | 180mg |
| Type | Intravenous powder for injection |
| Protein binding | SN-38, the active moiety, remains mostly bound to the IgG component in serum. In patients administered with 10 mg/kg of sacituzumab govitecan, free SN-38 serum levels were measured as 2.3% and 4.5% at 30 minutes and one day, respectively. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Sacituzumab Govitecan is sacituzumab govitecan targets TROP-2-expressing cancer cells through a humanized antibody (RS7) before subsequently becoming internalized and releasing the topoisomerase I inhibitor SN-38 to induce DNA damage-mediated apoptosis.[L13002]
Sacituzumab Govitecan is indicated for adult patients with metastatic triple-negative breast cancer (mTNBC) who have undergone two or more prior therapies for metastatic disease.
This indication has been approved under accelerated approval, and continued approval may be contingent on the demonstration of clinical benefit in confirmatory trials.
Sacituzumab Govitecan is also used to associated treatment for these conditions: Metastatic Triple-negative Breast Cancer
How Sacituzumab Govitecan works
Sacituzumab Govitecan is an antibody-drug conjugate (ADC) targeting TROP-2-expressing cancer cells to induce DNA-damage-mediated cell death. The conjugate comprises a humanized anti-TROP-2 monoclonal antibody (RS7-3G11, also known as RS7) chemically linked by a hydrolyzable CL2A linker to the cytotoxic drug SN-38.
The proposed mechanism of action first involves the binding of the RS7 component to TROP-2, which is highly expressed on the cell surface of multiple cancers. Binding of RS7 to TROP-2 results in rapid internalization of bound antibody, and the likely intracellular release of SN-38 via hydrolysis of the CL2A linker. SN-38 is an active metabolite of the anti-cancer drug irinotecan, which is thought to work primarily through inhibition of DNA topoisomerase I, leading to DNA damage and eventual cell death. In addition, recent work has identified a possible secondary mechanism of action for SN-38 by disrupting the binding of Far Upstream Binding Protein 1 (FUBP1) to the FUSE elements regulating oncogene expression.
In addition to SN-38-mediated cell death, there is also some evidence that the RS7 component of the conjugate drug possesses antibody-directed cellular toxicity.
Toxicity
Toxicity information regarding sacituzumab govitecan is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as neutropenia, diarrhea, hypersensitivity, nausea/vomiting, and other systemic effects related to cytotoxic drugs. Symptomatic and supportive measures are recommended.
Food Interaction
No interactions found.Volume of Distribution
Sacituzumab Govitecan has a mean volume of distribution of 0.045 L/kg.
Elimination Route
In patients receiving 10 mg/kg sacituzumab govitecan the Cmax of the conjugate was 243,000 ± 45,600 ng/mL while the Cmax of free SN-38 was 127 ± 60 ng/mL. Similarly, the AUC0-168 for the conjugate/free SN-38 was 5,210,000 ± 1,230,000 and 3,900 ± 1,830 ng*h/mL, respectively.
Half Life
Sacituzumab Govitecan has a mean half-life of 16 hours, while free SN-38 has a mean half-life of 18 hours.
Clearance
Sacituzumab Govitecan has a clearance rate of 0.002 L/h/kg.
Elimination Route
No detailed information exists for sacituzumab govitecan elimination; renal elimination of SN-38 is known to be minimal, and it is expected that the fecal route will be the major contributor.
Innovators Monograph
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