Breast cancer is the most common type of cancer in women, with more than 2 million cases being added each year worldwide. Triple-negative breast cancer (TNBC) accounts for approximately 12-20% of all breast cancers. TNBC is more common in women under 50 years of age compared with other types of breast cancer. TNBC specifically refers to the breast cancer in which estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) are negatively expressed. The 5-year survival rate is less than 15%. TNBC is ineffective for both hormone therapy and HER2-targeted therapy (such as Herceptin), and the choice of clinical treatment is very limited, mainly relying on chemotherapy. Currently, there are no standard care regimens available for patients with refractory mTNBC.

Why is it so hard to cure triple negative breast cancer?
Currently, treatments for breast cancer include surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, endocrine therapy, and targeted therapy. Since triple-negative breast cancer lacks expression of ER, PR, and HER2, this means that endocrine therapy and targeted therapy against Her-2 do not work for this type of cancer. Although triple-negative breast cancer is sensitive to chemotherapy, only about 20% of patients have good chemotherapy effects through routine adjuvant chemotherapy. Many studies have confirmed that triple-negative breast cancer is more sensitive to neoadjuvant chemotherapy, and its pathological complete remission rate is higher.

Would Sacituzumab govitecan be the first ADC drug to treat triple negative breast cancer?
Under such circumstances, Immunomedics, a biopharmaceutical company focused on developing monoclonal antibody-based therapies for cancer and other serious diseases as targeted therapies, has developed an antibody drug conjugate (ADC) drug - sacituzumab govitecan –for the treatment of metastatic triple-negative breast cancer (mTNBC). Recently, the company published an updated data review as a result of phase II clinical trials.

Sacituzumab govitecan is a novel, pioneered antibody drug conjugate (ADC) drug, coupled by a humanized IgG1 antibody targeting the TROP-2 antigen and SN-38, the metabolically active product of the chemotherapeutic drug irinotecan (a topoisomerase I inhibitor). TROP-2 is a cell surface glycoprotein expressed in more than 90% of TNBC.

Previously, industry analysts believe that sacituzumab govitecan represents a significant advancement compared to standard care based on Phase II clinical data that has been obtained. If approved, the drug will be the first and only ADC drug to treat mTNBC, with a peak sale of more than $1 billion as expected.

MTNBC patients have aggressive biological properties of the tumor, and the choices for effective treatment for patients who have previously received treatment are very limited. Standard chemotherapy is associated with low response rates and considerable toxicity, highlighting the need for better therapies in the clinic. Data from Phase II studies highlight potential new approaches to treating mTNBC and improving patient outcomes, which is expected to create a new treatment model.

Data showed that sacituzumab govitecan treatment: (1) the overall response rate based on local assessment was 33.3% (95% CI: 24.6-43.1), and the overall response rate based on blind independent center assessment (BICR) was 34.3% (95% CI: 25.4-44.0); (2) median duration of remission was 7.7 months (95% CI: 4.7-10.8, local assessment) and 9.1 months (95% CI: 4.6-11.3, BICR); (3) the median progression-free survival was 5.5 months (95% CI: 4.1-6.3).

Efficacy was also observed in patients who had previously received taxanes and anthracyclines, indicating a lack of cross-resistance to previous cytotoxic chemotherapy. The duration of sacituzumab govitecan treatment (5.1 months) was longer than the duration of the previous anti-tumor therapy treatment (2.5 months), further demonstrating the clinical activity in patients with refractory mTNBC.

It is worth mentioning that in January of this year, sacituzumab govitecan's biological product licensing application (BLA) encountered a complete FDA response letter (CRL). In the CRL, the FDA refused to approve sacituzumab govitecan on the grounds of manufacturing problems, which further delayed the regulatory schedule for the drug. The BLA is intended to apply for FDA’s accelerated approval of sacituzumab govitecan for mTNBC patients who have previously received at least 2 therapies for metastatic disease.

In addition to mTNBC, Immunomedics is planning a clinical study of sacituzumab govitecan for the treatment of other cancers, and two studies are recruiting patients: a critical phase II study (NCT03547973) is recruiting for treatment with platinum-containing chemotherapy or PD-(L)1 therapy in patients with metastatic urothelial carcinoma (mUC); a phase II study (NCT03725761) is recruiting patients with metastatic castration-resistant prostate cancer (mCRPC) who are undergoing second-generation androgen receptor-targeted therapy.

Introduction of Antibody drug conjugates
Antibody drug conjugates (ADCs) consist of recombinant monoclonal antibodies (mAbs) that are covalently bound to cytotoxic chemicals (also called ADC Cytotoxin) through synthetic linkers. Therefore, ADCs not only have the anti-tumor efficacy of highly cytotoxic small molecule drugs, but also successfully combine the high selectivity, stability and favorable pharmacokinetic characteristics of the mAb.

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This article is written by staff from BOC Sciences.