Gilead’s Trodelvy (Sacituzumab Govitecan) Receives Fifth Regulatory Approval via Project Orbis for Metastatic Triple-Negative Breast Cancer, Demonstrating Significant Survival Benefit

October 11, 2021 /BioonBIOON/ -- Gilead Sciences (Gilead) recently announced that Health Canada has approved its targeted anticancer drug through Project Orbis.Trodelvy (sacituzumab govitecan-hziy), for the treatment of metastatic triple-negativeBreast Cancer(mTNBC) Adult Patients. This drug is specifically indicated for: adult patients with unresectable locally advanced or metastatic TNBC who have previously received at least two prior therapies, including at least one for metastatic disease.Trodelvy is a novel first-in-class Trop-2-targeted antibody-drug conjugate (ADC).. Trop-2 is a cell surface protein overexpressed in TNBC and other solid tumors.

It is worth noting that,Trodelvy is the first therapy to demonstrate superiority over standard of care in the treatment of metastatic TNBC, marking a significant advance in TNBC treatment.. In the Phase 3 ASCENT study,Compared with chemotherapy, Trodelvy significantly prolonged progression-free survival (median PFS: 4.8 months vs. 1.7 months), significantly reducing the risk of disease progression or death by 57% (HR=0.43, p<0.0001), regardless of brain metastasis status. Furthermore, compared with chemotherapy, Trodelvy significantly prolonged overall survival (median OS: 11.8 months vs. 6.9 months), significantly reducing the risk of death by 49% (HR=0.51, p<0.0001).

ThisThis Canadian approval also marks the fifth approval for Trodelvy granted through the Orbis Project.. Previously, Trodelvy had already received approval in the United States, Switzerland, the United Kingdom, and Australia through the Orbis program. Orbis is a program launched in September 2019 by the Oncology Center of Excellence (OCE) of the U.S. Food and Drug Administration (FDA), aimed at the United StatesFDAand its regulatory authorities for international cooperation provide a ... targetingTumorA collaborative framework for joint product submission and review accelerates the review process, enabling simultaneous approval of oncology drug applications across different countries. In addition to regulatory approval under Project Orbis, the European Medicines Agency (EMA) accepted the Marketing Authorization Application (MAA) for Trodelvy in March of this year. Furthermore,Through its licensing partner, Everest Medicines, Trodelvy is also under regulatory review in China and Singapore.

Dr. Merdad Parsey, Chief Medical Officer of Gilead Sciences, Inc., stated: “As Trodelvy is the first and only targeted therapy to demonstrate superior overall survival compared to chemotherapy in the second-line treatment of metastatic triple-negative breast cancer (TNBC), it is imperative to ensure eligible patients have access to Trodelvy. We are pursuing innovative regulatory pathways, such as those provided by the Orbis Program, to help patients access Trodelvy as quickly as possible.”

Trodelvy is a novel, first-in-class antibody-drug conjugate (ADC) targeting Trop-2. It consists of a humanized IgG1 antibody targeting the TROP-2 antigen conjugated to SN-38, the active metabolite of the chemotherapeutic agent irinotecan (a topoisomerase I inhibitor), with a drug-to-antibody ratio (DAR) of up to 7.6:1. Trop-2 is a protein expressed in many epithelialTumorA cell surface protein frequently expressed in (including TNBC), is expressed in over 90% of TNBC cases. Trodelvy specifically binds to Trop-2 and delivers the anticancer agent SN-38 to kill cancer cells.

Trodelvy was developed by Immunomedics, and the core of its proprietary ADC platform is the use of a novel linker that does not require enzymatic cleavage to release the payload, and can function within tumor cells andTumordeliver active drugs into the microenvironment, thereby inducing a bystander effect. In April 2019,Everest Medicines (Everest Medicines)An agreement was signed with Immunomedics to secure the rights to Trodelvy in Greater China, South Korea, Mongolia, and Southeast Asian countries and regions. In September 2020, Gilead Sciences acquired Immunomedics for $21 billion, adding Trodelvy to its portfolio.

In the United States, Trodelvy has been approved for 2 indications:（1）For the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have previously received at least two prior therapies, at least one of which was for metastatic disease.；（2）Indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.

In China, Trodelvy (sacituzumab govitecan) was included in the 2020 edition of the 《Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer in China》 in October 2020. The guidelines were formulated by the Breast Cancer Expert Committee of the National Cancer Quality Control Center, the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association, and the Chinese Anti-Cancer AssociationTumorJointly compiled by the Professional Committee on Clinical Drug Research. May 2021,The National Medical Products Administration (NMPA) has accepted the biologics marketing authorization application for Trodelvy and designated it for priority review.

Breast cancer is the most common type of cancer in women, with over 2 million new cases diagnosed globally each year. Triple-negative breast cancer (TNBC) accounts for approximately 15% of all breast cancer cases. Compared to other breast cancer subtypes, TNBC is more prevalent in women under 50 years of age. TNBC specifically refers to breast cancers that test negative for estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2). It progresses rapidly, carries a poor prognosis, and has a 5-year survival rate of less than 15%. TNBC is unresponsive to both hormone therapy and HER2-targeted therapies (such as Roche's Herceptin), leaving clinical treatment options highly limited and primarily reliant on chemotherapy.

Regulatory approval for Trodelvy was based on the results of the Phase 3 ASCENT (NCT02574455) trial. This was an international, open-label Phase III study that enrolled more than 500 patients with mTNBC who had previously received at least two prior therapies for metastatic disease. In the study, patients were randomized into two groups: one received Trodelvy and the other received physician's-choice chemotherapy. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DOR), time to response, safety, and tolerability.

The results demonstrated that the study met both the primary and key secondary endpoints: compared with chemotherapy, the Trodelvy group showed a statistically significant improvement in progression-free survival (PFS) (median PFS: 4.7 months vs. 1.7 months), with a statistically significant 57% reduction in the risk of disease progression (HR=0.43; 95% CI: 0.35–0.54; p<0.0001). Furthermore, the study also met the key secondary endpoint for overall survival (OS): compared with chemotherapy, the Trodelvy group demonstrated a statistically significant improvement in OS (median OS: 11.8 months vs. 6.9 months), with a statistically significant 49% reduction in the risk of death (HR=0.51; 95% CI: 0.41–0.62; p<0.0001). Additionally, the objective response rate (ORR) was significantly higher in the Trodelvy group compared with the chemotherapy group (35% vs. 5%). (Bioon.com)

Original Source:Gilead Marks Fifth Approval for Trodelvy in Metastatic Triple-Negative Breast Cancer Under Project Orbis Initiative with Health Canada Authorization