Everest Medicines and Gilead’s Trodelvy (Sacituzumab Govitecan) Achieves 38.8% ORR in Chinese Phase 2b Trial for Metastatic Triple-Negative Breast Cancer

November 11, 2021 /BioValleyBIOON/ -- Gilead Sciences recently announced that in the partner Everest Medicines-sponsored Phase 2b EVER-132-001 study, the targeted anticancer drug Trodelvy (sacituzumab govitecan-hziy) treated metastatic triple-negativeBreast Cancer(mTNBC) achieved the primary endpoint of overall response rate (ORR).

TNBC is the most aggressive type of breast cancer, accounting for approximately 15% of all breast cancer cases and is more common in younger and premenopausal women. TNBC specifically refers to breast cancer that tests negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). Compared with other types of breast cancer, treatment options for TNBC are extremely limited. The average time to recurrence and metastasis for TNBC is 2.6 years, while for other breast cancers it is 5 years. In patients with metastatic TNBC, the 5-year survival rate is 12%, compared to 28% for other types of metastatic breast cancer.

Trodelvy is a novel first-in-class antibody-drug conjugate (ADC) targeting Trop-2, a protein located on the cell surface, which is highly expressed in TNBC and many otherTumorOverexpressed in China. To date, Trodelvy has been approved in the United States, Switzerland, the United Kingdom, Australia, and Canada for the treatment of TNBC. In addition,Through its licensed partner Cloudtop New Peak, Trodelvy is also undergoing regulatory review in China and Singapore.

EVER-132-001 is a single-arm, multicenter Phase 2b registrational study evaluating the efficacy and safety of Trodelvy in the treatment of TNBC. The studyEnrolled 80 patients with unresectable locally advanced or metastatic TNBC in ChinaThese patients had previously received at least two systemic treatments, with at least one for metastatic disease. The primary endpoint was the overall response rate (ORR), assessed by an independent review committee (IRC) according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The results showed,The overall response rate (ORR) assessed by the IRC was 38.8% (CI:95%)..Trodelvy's safety profile was consistent with that reported in prior studies, with no new safety signals identified. The study'sORR results were consistent with the findings from the global Phase 3 ASCENT (NCT02574455) study (ORR=35%).Consistent.

It is worth mentioning that,Trodelvy is the first therapy to demonstrate superiority over standard care in the treatment of metastatic TNBC, marking a significant advancement in the treatment of TNBC.In the global Phase 3 ASCENT study, compared with chemotherapy, Trodelvy significantly prolonged progression-free survival (median PFS: 4.8 months vs 1.7 months) and significantly reduced the risk of disease progression or death by 57% (HR=0.43, p<0.0001), regardless of whether brain metastases were present. In addition, compared with chemotherapy, Trodelvy significantly extended overall survival (median OS: 11.8 months vs 6.9 months) and significantly reduced the risk of death by 49% (HR=0.51, p<0.0001). Furthermore, the ORR in the Trodelvy group was significantly higher than that in the chemotherapy group (35% vs 5%).

Trodelvy Structural Features (Source: broadpharm.com)

Trodelvy is a novel, first-of-its-kind antibody-drug conjugate (ADC) targeting Trop-2, composed of a humanized IgG1 antibody targeting the TROP-2 antigen conjugated with SN-38, the metabolically active product of the chemotherapy drug irinotecan (a topoisomerase I inhibitor), with a drug-to-antibody ratio as high as 7.6:1. Trop-2 is a type of epithelialTumor(including TNBC) is a cell surface protein frequently expressed in over 90% of TNBC. Trodelvy targets and binds to Trop-2, delivering the anticancer agent SN-38 to kill cancer cells.

Trodelvy, developed by Immunomedics, is based on its proprietary ADC platform, which utilizes a novel linker that does not require enzymes to release the payload and can function within tumor cells.TumorDelivery of active drugs in the microenvironment, thereby generating a bystander effect. In April 2019, Everest Medicines entered into an agreement with Immunomedics to obtain 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, bringing Trodelvy into 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 TNBC who have received at least 2 prior therapies, with at least 1 therapy for metastatic disease; (2) for the treatment of adult patients with locally advanced or metastatic urothelial cancer (UC) who have previously received platinum-containing chemotherapy and a PD-1 inhibitor or PD-L1 inhibitor.

In China, Trodelvy (Sacituzumab Govitecan) was included in the 2020 edition of the "Chinese Guidelines for Standardized Diagnosis and Treatment of Advanced Breast Cancer" in October 2020. These guidelines were developed by the Breast Cancer Expert Committee of the National Cancer Control Center, the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association, and the Chinese Anti-Cancer Association.TumorCo-authored by the Professional Committee of Drug Clinical Research.In May 2021, the National Medical Products Administration (NMPA) accepted the Biologics License Application for Trodelvy and granted it priority review.: For the treatment of adult patients with unresectable locally advanced or metastatic TNBC who have received at least two systemic therapies (at least one for metastatic disease). (Bioon.com)

Source of the original text:Everest Medicines and Gilead Sciences Jointly Announce Phase 2b Study of Sacituzumab Govitecan Conducted in China of Patients With Metastatic Triple-negative Breast Cancer Meets Primary Overall Response Rate Endpoint