Gilead's Trodelvy Demonstrates Significant Survival and Quality-of-Life Benefits in Phase 3 ASCENT Study for Metastatic Triple-Negative Breast Cancer

News on June 10, 2022 /BioValleyBIOON/ -- Gilead Sciences recently at the 2022 American Society of Clinical Oncology (ASCO) The final data of the Phase 3 ASCENT study on Trodelvy (sacituzumab govitecan), a Trop-2 targeted antibody-drug conjugate, was announced at the annual meeting. The study involved patients with recurrent or refractory metastatic triple-negative breast cancer who had previously received at least two systemic treatments (with at least one treatment for metastatic disease).Breast Cancer(TNBC) patients, comparing Trodelvy with a single-agent chemotherapy regimen chosen by the physician.

The final database lock follow-up analysis showed,In the intent-to-treat (ITT) population, compared with physician's choice of chemotherapy, Trodelvy extended the median progression-free survival (mPFS: 4.8 months vs 1.7 months; HR=0.41; p<0.0001) and prolonged the median overall survival (mOS) by nearly 5 months (11.8 months vs 6.9 months; HR=0.51; p<0.0001).The 2-year OS rate in the Trodelvy treatment group was 20.5% (95% CI: 15.4-26.1), while the 2-year OS rate in the chemotherapy group was 5.5% (95% CI: 2.8-9.4).

In addition,Compared with chemotherapy, Trodelvy in health-relatedQuality of Life(HRQoL) also showed clinically meaningful improvements。Metastatic TNBC is often associated with a significant decline in quality of life., patients may undergo multiple rounds of intensive chemotherapy, making the assessment of symptom burden particularly crucial in this context.Compared with chemotherapy, Trodelvy showed clinically meaningful improvements in all five major HRQoL domains., including the following aspects of changes relative to baseline:Overall health status (-5.8 vs -9.4), physical function (-4.6 vs -13.5), role function (-8.4 vs -18.8), fatigue (5.1 vs 14.0), pain (2.8 vs 6.8).

The safety profile of Trodelvy was consistent with previous reports. Key grade ≥3 treatment-related adverse events for Trodelvy compared to chemotherapy were diarrhea (11% vs <1%), neutropenia (52% vs 33%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%). Treatment discontinuation due to adverse events was ≤3% in both groups. The U.S. prescribing information for Trodelvy includes a Boxed Warning regarding severe or life-threatening neutropenia and severe diarrhea.

Aditya Bardia, global chief investigator of the ASCENT study, director of the breast cancer research program at the Massachusetts General Hospital Cancer Center, and associate professor of medicine at Harvard Medical School, stated:These final data from the Phase 3 ASCENT study confirm the overall survival and quality of life benefits of Trodelvy compared to traditional chemotherapy for patients with previously treated metastatic triple-negative breast cancer."So far, effective treatment options often have a significant impact on the quality of life and lead to poor prognosis for these patients."

Bill Grossman, Head of Oncology Therapeutic Area and Senior Vice President of Gilead Sciences, said: "Trodelvy is the cornerstone of our solid tumor portfolio,This drug is the first and only one that has shown overall survival and quality of life benefits compared to single-agent chemotherapy in second-line metastatic TNBC patients.StatisticsSignificantly Improved Antibody-Drug Conjugates"These final data from the ASCENT study reinforce the importance of Trodelvy as a new standard-of-care option in this setting."

Trodelvy Structural Features (Source: broadpharm.com)

Triple-Negative Breast Cancer (TNBC) is a highly aggressive form of breast cancer, accounting for approximately 15% of all breast cancer cases. It is more common in younger and premenopausal women and is more prevalent among Black and Hispanic women. TNBC tumors lack sufficient expression of estrogen, progesterone, or HER2 receptors, rendering endocrine therapy or HER2-targeted treatments largely ineffective.The treatment of metastatic TNBC is particularly challenging, with a 5-year survival rate of approximately 12%., while the 5-year survival rate for patients with other types of metastatic breast cancer is approximately 28%.The poor prognosis of TNBC is often accompanied by a significant decline in quality of life, especially in recurrent/refractory disease.。

Trodelvy is a first-in-class 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 cell surface antigen overexpressed in many epithelial tumors, including TNBC, and is expressed in over 90% of TNBC cases. Trodelvy binds to Trop-2 and delivers the anti-cancer agent SN-38 to kill cancer cells.

Trodelvy, developed by Immunomedics, is based on a proprietary ADC platform that utilizes a novel linker (cleavable linker). This linker does not require enzymes to release the payload and can deliver the active drug within tumor cells and the tumor microenvironment, 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, and certain Southeast Asian countries. 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 previously received at least 2 therapies, including at least 1 therapy for metastatic disease.；（2）For the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who have previously received platinum-based chemotherapy and PD-1 inhibitor or PD-L1 inhibitor therapy.

In China, Trodelvy (Sacituzumab Govitecan) was included in the 2020 edition of "China Guidelines for the Treatment of Advanced Breast Cancer" in October 2020.Diagnosis and TreatmentGuidelines》, in October 2021, it was included in the "Guidelines and Norms for Diagnosis and Treatment of Breast Cancer by the Chinese Anti-Cancer Association (2021)." In May 2021,China's National Medical Products Administration (NMPA) has accepted the Biologics License Application for Trodelvy and included it in the priority review.. (Bioon.com)

Source of the original text:Final Data From Phase 3 ASCENT Study Demonstrates Trodelvy Extends Overall Survival Over Chemotherapy in Second-Line Metastatic TNBC