Trodelvy (Sacituzumab Govitecan) Shows Significant Survival Benefit in Metastatic Triple-Negative Breast Cancer Regardless of Initial HR/HER2 Status

September 16, 2021 /BioonBIOON/ -- Gilead Sciences recently at the 2020 European Medical# Tumorpresented at the European Society for Medical Oncology (ESMO) Virtual CongressAntibody-Drug Conjugate (ADC) Trodelvy (sacituzumab govitecan-hziy, sacituzumab govitecan) for the Treatment of Triple-NegativeBreast Cancer（TNBC）New data from the Phase 3 ASCENT study (NCT02574455). ASCENT is an international, open-label, Phase 3 study that enrolled more than 500 patients with relapsed or refractory metastatic TNBC who had previously received at least two prior therapies, at least one of which was for metastatic disease. In the study, patients were randomized into two groups: one receiving Trodelvy and the other receiving physician's choice of chemotherapy.

This timeConferenceA retrospective subgroup analysis presented at [...] showed:In patients not initially diagnosed with TNBC, Trodelvy improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared with chemotherapy.In the metastatic stage of breast cancer, it is not uncommon for patients to transition from one subtype to another.In the ASCENT study, approximately one-third of TNBC patients were initially notDiagnosisFor TNBC, compared with chemotherapy, Trodelvy provides a survival benefit for these patients. For treating physicians,These data further support the efficacy of Trodelvy in more complex patients.

This analysis, presented at the conference, included 146 patientsPatients negative for brain metastasis who are eligible for chemotherapy, their initialDiagnosisfor non-TNBC breast cancer, among whom 70 were treated with Trodelvy and 76 received physician's choice of chemotherapy. Among these patients,Compared with chemotherapy, Trodelvy improved median PFS (4.6 months vs. 2.3 months; HR: 0.48; P=0.0004), median OS (12.4 months vs. 6.7 months; HR: 0.44; P<0.0001), and ORR (31% vs. 4%). The results in this subgroup were consistent with those of the overall ASCENT study population.

In this subgroup, the safety of Trodelvy was consistent with the previously reported ASCENT study. Compared with chemotherapy, key treatment-related grade ≥3 adverse events with Trodelvy were: neutropenia (59% vs 40%), leukopenia (12% vs 9%),Anemia(8% vs 7%) and diarrhea (7% vs 0%). There were no treatment-related deaths with Trodelvy. The US Prescribing Information for Trodelvy includes a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea.

Gilead SciencesTumorDr. Bill Grossman, Senior Vice President of Clinical Research, stated: “Trodelvy is already changing the prognosis for patients with second-line or advanced metastatic TNBC. We are committed to ongoing research to further characterize the clinical profile of Trodelvy. Therefore, we are pleased to initially un...DiagnosisThis subgroup analysis conducted in patients with TNBC showed: overall survival, progression-free survival, and response rate were similar to those observed in the overall ASCENT study population.”

Trodelvy (sacituzumab govitecan) 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 within tumor cells andTumordelivering active drugs within the microenvironment, thereby inducing a bystander effect. In April 2019,Everest MedicinesEntered into an agreement 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, bringing Trodelvy into its portfolio.

Currently, Trodelvy is marketed in the United States. In China, in October 2020, Trodelvy (sacituzumab govitecan) was included in the 2020 edition of 《Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer in China》, which was jointly formulated by the Breast Cancer Expert Committee of the National Cancer Quality Control Center, the Breast Cancer Professional Committee of the China Anti-Cancer Association, and the China Anti-Cancer Association.TumorJointly compiled by the Professional Committee on Clinical Drug Research.In May 2021, the National Medical Products Administration (NMPA) accepted the Biologics License Application (BLA) for Trodelvy.

Notably,Trodelvy is the first therapy to improve progression-free survival (PFS) and overall survival (OS) in patients with metastatic TNBC, marking a significant advancement in the treatment of TNBC.In the Phase III ASCENT study, compared with chemotherapy, Trodelvy significantly prolonged PFS (median PFS: 4.8 months vs 1.7 months), significantly reduced the risk of disease progression or death by 57% (HR=0.43, p<0.0001), significantly prolonged OS (median OS: 11.8 months vs 6.9 months), significantly reduced the risk of death by 49% (HR=0.51, p<0.0001), and significantly improved the overall response rate (ORR: 35% vs 5%).

Triple-negative breast cancer (TNBC) is a highly aggressive disease, accounting for approximately 15% of all breast cancer cases globally. In Asia, the median age at diagnosis for breast cancer shows a trend toward younger ages compared to Western countries, and over the past decade, the proportion of the TNBC molecular subtype has been gradually increasing. TNBCTumorDue to the lack of sufficient expression of estrogen, progesterone, or HER2 receptors, endocrine therapy and HER2-targeted therapy are largely ineffective. Over the past two decades, the overall survival of patients with TNBC has not improved, underscoring an urgent need to develop novel and effective treatment options.

Trodelvy is a novel, first-in-class antibody-drug conjugate (ADC) targeting Trop-2, comprising a humanized IgG1 antibody targeting the TROP-2 antigen conjugated to SN-38, the metabolically active derivative of the chemotherapeutic agent irinotecan (a topoisomerase I inhibitor), with a drug-to-antibody ratio as high as 7.6:1. Trop-2 is a ... in many epithelial# TumorA cell surface protein frequently expressed in various malignancies, including metastatic triple-negative breast cancer (mTNBC) and metastatic urothelial carcinoma (mUC), whose high expression is associated with high recurrence rates and low survival rates. Trodelvy specifically binds to Trop-2 and delivers the anticancer agent SN-38 to kill cancer cells.

Trodelvy received US approval in April 2020FDAAccelerated approval, and received full approval in April 2021, for the treatment of: adult patients with unresectable locally advanced or metastatic TNBC who have previously received at least two therapies, at least one of which was for metastatic disease.

In April 2021, Trodelvy again received USFDAApproval of a new indication 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 inhibitor or a PD-L1 inhibitor.

Currently, an application for a new indication for Trodelvy is also under review by the U.S.FDAReview: 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 the neoadjuvant/adjuvant or metastatic setting.

Trodelvy is also being developed for the treatment of HR+/HER2- metastatic breast cancer and metastatic non-small cell lung cancer (NSCLC), and additional evaluations for various solid tumors are also underway. (Bioon.com)

Source:New Data Demonstrate Trodelvy® Survival Benefit in Metastatic Triple-Negative Breast Cancer Patients Regardless of Initial HR/HER2 Status