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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Finally, the results of other clinical trials suggest that sacituzumab govitecan is active in other solid tumors, producing partial responses in patients with colorectal, esophageal, small-cell and non-small-cell lung and urinary bladder cancers.
Sacituzumab for the treatment of triple-negative breast cancer: the poster child of future therapy?
Published in Expert Opinion on Investigational Drugs, 2019
Mark L. Zangardi, Laura M. Spring, Aiko Nagayama, Aditya Bardia
The safety and PK of sacituzumab govitecan in patients with various pretreated metastatic epithelial cancers were investigated in a phase I/II study [19]. In the phase II component of the study, sacituzumab govitecan was administered at starting doses of either 8 mg/kg or 10 mg/kg intravenously (IV) on days 1 and 8 of 21-day cycles. Peak antibody concentrations tended to increase proportionally with continued treatment in the 10 mg/kg group. Levels were largely cleared within 3 days, and SN-38 was released gradually at a rate of about 50% per day. Only about 2.5% of the total SN-38 was free; the majority remained bound to the antibody following administration of sacituzumab govitecan. Similar levels of total and free SN-38G (an inactive metabolite of SN-38) [17] were apparent and were lower than levels of SN-38, suggesting that SN-38 is protected from glucuronidation when bound to the antibody. The half-life of sacituzumab govitecan was approximately 11–14 h, whereas the half-life of the antibody was approximately 103–114 h. Clearance rates were similar between patients with different tumor types [19].
Optimizing outcomes and managing adverse events in locally advanced or metastatic urothelial cancer: a clinical pharmacology perspective
Published in Expert Review of Clinical Pharmacology, 2023
Pratap Singh, Anand Rotte, Anthony A. Golsorkhi, Sandhya Girish
ADCs are another class of drugs that drastically influenced cancer treatment and research. They typically consist of a cytotoxic payload linked to a monoclonal antibody against proteins expressed specifically on tumor cells. Main advantage of ADCs over conventional chemotherapy is the specificity achieved through targeted delivery of cytotoxic drugs through monoclonal antibodies [37]. Two monoclonal antibodies including enfortumab vedotin and sacituzumab govitecan have been fully and conditionally approved for the treatment of mUC as second and third-line therapies respectively. Enfortumab vedotin is comprised of a fully human anti-Nectin-4 IgG1 kappa monoclonal antibody (AGS-22C3) conjugated to monomethyl auristatin E (MMAE), a small molecule microtubule disrupting agent, via a protease-cleavable maleimidocaproyl valine-citrulline (vc) linker (SGD-1006). It is recommended as second-line treatment for mUC after chemotherapy and in cisplatin ineligible patients progressing after first-line immune checkpoint blockers [28]. Sacituzumab govitecan consists of anti-Trop2 (trophoblast cell-surface antigen-2) humanized monoclonal IgG1κ antibody (hRS7) conjugated to SN-38, a topoisomerase inhibitor through a hydrolysable linker (CL2A). Sacituzumab govitecan is approved for mUC patients progressing after a platinum-containing chemotherapy and immune checkpoint blocker (either anti-PD-1 or anti-PD-L1) treatment. Recommended dose for enfortumab vedotin is 1.25 mg/kg (up to a maximum dose of 125 mg) given as an IV infusion over 30 minutes on Days 1, 8, and 15 of a 28-day cycle. Recommended dose of sacituzumab govitecan is 10 mg/kg IV infusion on Days 1 and 8 of continuous 21-day treatment cycles given until disease progression or unacceptable toxicity.
Tackling metastatic triple-negative breast cancer with sacituzumab govitecan
Published in Expert Review of Anticancer Therapy, 2021
Anna R Schreiber, Michelle Andress, Jennifer R Diamond
Sacituzumab govitecan also showed impressive clinical benefit when compared to single-agent standard-of-care anti-cancer agents. Patients who had previously received a PD-1 or PD-L1 inhibitor found benefit with sacituzumab govitecan with a PFS of 4.2 [95% CI 3.2–5.6] compared to 1.6 [95% CI 1.4–2.3] in the chemotherapy group [45]. In addition, when compared to single-arm chemotherapy, sacituzumab govitecan again showed benefit with an ORR of 35% compared to just 5% for the chemotherapy group [45]. This highlights the possible utility and benefit of using sacituzumab govitecan in a heavily pre-treated mTNBC population.