ADC Drug Trodelvy Shows Positive Efficacy In three Types of Cancers

1. Biochempeg https://www.biochempeg.com ADC Drug Trodelvy Shows Positive Efficacy In three Types of Cancers On October 28, Gilead Sciences, Inc. announced that it had reached a clinical trial cooperation and supply agreement with Merck & Co., Inc. to evaluate the efficacy of Gilead’s Trop-2 targeting antibody-drug conjugate (ADC) Trodelvy in combination with Merck’s anti-PD-1 therapy, Keytruda (pembrolizumab), as a first-line therapy for locally advanced or metastatic triple-negative breast cancers (TNBC). What is Trodelvy (Sacituzumab govitecan-hziy)? Trodelvy (chemical name: sacituzumab govitecan-hziy), a first-in-class Trop-2 directed antibody-drug conjugate, which was first approved by the FDA for accelerated marketing on April 22, 2020, for unresectable locally advanced or metastatic TNBC that has received two or more systemic treatments and is the first ADC drug approved by the FDA for the treatment of TNBC. On April 7, 2021, Trodelvy was fully approved by the FDA for the treatment of TNBC. So far, Trodelvy has been approved in the United States, Switzerland, the United Kingdom, Australia, and Canada for the treatment of TNBC. In addition, Trodelvy is also undergoing regulatory review in China and Singapore. It is worth mentioning that Trodelvy is the first therapy to show superiority to standard care in the treatment of metastatic TNBC, marking a major advancement in the treatment of TNBC.

2. Biochempeg https://www.biochempeg.com The active pharmaceutical ingredient of Trodelvy is sacituzumab govitecan, which is formed by coupling a humanized IgG1 antibody targeting the Trop-2 antigen and the metabolically active product SN-38 of the chemotherapy drug Irinotecan (a topoisomerase I inhibitor). The drug-antibody ratio is as high as 7.6:1. Trop-2 is a cell surface protein expressed in many solid tumors and is expressed in more than 90% of TNBC. Trodelvy targets Trop-2 and delivers the anti-cancer agent SN-38 to kill cancer cells. What Is Trodelvy (Sacituzumab govitecan-hziy) composed of? Trodelvy (Sacituzumab govitecan-hziy) is an immune targeted therapy drug. It is made up of the following three components: 1. Sacituzumab, a molecule called a monoclonal antibody, targets the Trop-2 protein. Trop-2 protein is found in more than 90% of triple-negative breast cancers 2. SN-38, a topoisomerase I inhibitor chemotherapy; topoisomerase I inhibitor works by

3. Biochempeg https://www.biochempeg.com interfering with the replication ability of cancer cells 3. A compound that links sacituzumab to SN-38. 2-((Azido-PEG8-carbamoyl)methoxy)acetic acid (CAS No.: 846549-37-9) is a PEG product that links Sacituzumab to SN-38. How Trodelvy (sacituzumab govitecan-hziy) works? Trodelvy (sacituzumab govitecan-hziy) is a type of targeted therapy called an antibody drug conjugate. It works by delivering a chemotherapy drug directly to the cancer cell which keeps it from growing and spreading. Trop-2 is a cell surface protein expressed in many solid tumors and is expressed in more than 90% of TNBC. As we mentioned above, Sacituzumab is one of the compounds that make up Trodelvy. It targets and attaches to the Trop-2 protein. SN-38 is the chemotherapy part of Trodelvy's topoisomerase I inhibitor. Like other chemotherapy drugs, it interferes with the ability of cells to replicate. SN-38 is not a targeted drug, which means it can affect healthy cells and cancer cells. Trodelvy aims to deliver SN-38 chemotherapy drugs to cancer cells in a targeted manner by attaching SN-38 to sacituzumab. Then sacituzumab carries SN-38 to triple-negative cancer cells. In this way, SN-38 is less toxic to healthy cells and is more effective in treating cancer cells. Which cancers could Trodelvy (Sacituzumab govitecan-hziy) be used to treat?

4. Biochempeg https://www.biochempeg.com Trodelvy is a new antibody-conjugated drug targeting Trop2. It has potential curative effects on cancers with high Trop2 expression. High Trop2 expression is common in multiple solid tumors such as triple-negative breast cancer, lung cancer, bladder cancer, and bowel cancer. Therefore, the drug has shown good curative effect in this series of cancers. schematic diagram of Trodelvy Triple negative breast cancer: In April 2020, the FDA approved this drug for advanced triple negative breast cancer based on data from a phase 2 clinical trial involving dozens of patients, with an effective rate of 34.3%, control rate of 69.5%, and median maintenance time of efficacy of 9.1 months. The award of full marketing status in this case is due to the perfect success of the Phase 3 clinical trial. An international multicenter phase 3 clinical trial of 529 patients with advanced refractory triple negative breast cancer who had failed standard treatment was conducted in 1:1

5. Biochempeg https://www.biochempeg.com groups. One group received Trodelvy, while the other group received chemotherapy of the physician's choice. The results showed that Trodelvy significantly prolonged the survival period. The median overall survival period was extended from 6.9 months to 11.8 months, which is equivalent to a 48% reduction in the patient's risk of death. Lung cancer: A clinical trial of 53 patients with advanced small-cell lung cancer who had failed first-line chemotherapy showed that Trodelvy was 15% effective in second-line treatment of advanced small-cell lung cancer, with tumor shrinkage in 60% of patients. Another clinical trial of 54 patients with advanced non-small cell lung cancer showed significant tumor shrinkage in 10 patients, with an effective rate of 19%. There were also 13 patients whose tumors were stable and non-progressive, and the disease control rate was as high as 43% (of 54 patients, 18 patients had received PD1 treatment before enrollment, but failed, 14 were evaluable after Trodelvy, 2 had significant tumor shrinkage, and 7 had stable disease, with a control rate of 64%).

6. Biochempeg https://www.biochempeg.com Bladder cancer: 45 patients were enrolled, and 14 patients were objectively effective after treatment, including 2 patients whose tumors completely disappeared. It is worth mentioning that among the 45 patients, 17 patients had failed PD1 treatment before enrollment, and after received Trodelvy treatment, the effective rate was 23.5%; of them, 15 patients with liver metastases, after received Trodelvy treatment, the effective rate was 33.3%. Urothelial carcinoma (UC), also known as transitional cell carcinoma (TCC), is the most common type of bladder cancer, accounting for approximately 90% of bladder cancers. On April 13, 2021, Trodelvy received accelerated approval by the FDA to treat sBLA for the second indication of locally advanced or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and PD-1/L1 inhibitors. In conclusion, Trodelvy has potential therapeutic effects on all types of solid tumors with high TROP2 expression. Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Biopharma PEG is dedicated to being your most reliable partner to provide high-quality PEG linkers to promote the progress of your ADC R&D. PEG product 2-((Azido-PEG8-carbamoyl)methoxy)acetic acid (CAS No.: 846549-37-9) acts as a PEG linker in the ADC drug Trodelvy that links Sacituzumab to SN-38. References： [1] Sacituzumab Govitecan Receives Positive CHMP Opinion as 2L Treatment for Adult Patients With Metastatic Triple-Negative Breast Cancer [2] https://www.breastcancer.org/treatment/targeted_therapies/trodelvy [3] Promise of ADCs in solid tumours: Immunomedics partners with Roche