Gilead's Trodelvy Receives Full FDA Approval for Metastatic Triple-Negative Breast Cancer

Compiled by Fan Dongdong

Gilead Sciences Announces Full FDA Approval of Targeted Anti-Cancer Drug Trodelvy for Adult Patients with Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer (TNBC) Who Have Previously Received Two or More Prior Systemic Therapies, Including at Least One for Metastatic Disease

The approval of Trodelvy was supported by data from the global, open-label, Phase III ASCENT trial. Results from the ASCENT trial demonstrated a clinically meaningful and statistically significant reduction in the risk of disease progression or death among patients treated with Trodelvy. The median progression-free survival (PFS) increased from 1.7 months with chemotherapy to 4.8 months with Trodelvy (HR: 0.43; 95% CI: 0.35–0.54; p < 0.0001), representing a 57% reduction in risk. Furthermore, the median overall survival (OS) for patients receiving Trodelvy was extended from 6.9 months to 11.8 months (HR: 0.51; 95% CI: 0.41–0.62; p < 0.0001), indicating that Trodelvy treatment reduces the risk of death by 49%.

Regarding safety, among all patients in the ASCENT trial (n = 482), the safety profile of Trodelvy demonstrated in the trial results was consistent with that described in the labels for other indications previously approved by the FDA. Compared with single-agent chemotherapy, the most common grade ≥3 adverse reactions associated with Trodelvy were neutropenia (52% vs. 34%), diarrhea (11% vs. 1%), leukopenia (11% vs. 6%), and anemia (9% vs. 6%). The proportion of patients treated with Trodelvy who experienced adverse reactions ultimately leading to treatment discontinuation was 5%.

Trodelvy is a novel, first-in-class antibody-drug conjugate (ADC) targeting Trop-2, with the active pharmaceutical ingredient sacituzumab govitecan. It consists of a humanized IgG1 antibody targeting the TROP-2 antigen conjugated to SN-38, the metabolically active product of the chemotherapy drug irinotecan (a topoisomerase I inhibitor). The drug was initially developed by Immunomedics. In September 2020, Gilead Sciences acquired Immunomedics for $21 billion, bringing Trodelvy into its portfolio. Trop-2 is a cell surface protein expressed in many solid tumors and in over 90% of triple-negative breast cancer (TNBC) cases. By binding specifically to Trop-2 and delivering the anticancer agent SN-38, Trodelvy achieves the effect of eliminating tumor cells.

Furthermore, a new indication application for Trodelvy is under review by the U.S. FDA, seeking approval for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who have previously received platinum-based chemotherapy and a PD-1 inhibitor or PD-L1 inhibitor in the neoadjuvant/adjuvant or metastatic setting.

In addition to receiving favorable news in the US market, Trodelvy is also expected to make progress in the European Union. In late March, the European Medicines Agency (EMA) accepted the Marketing Authorization Application (MAA) for Trodelvy for this indication. The acceptance was based on the positive results from the Phase 3 ASCENT clinical trial. Furthermore, regulatory reviews of Trodelvy are underway in the United Kingdom, Canada, Switzerland, and Australia. Through collaboration with Everest Medicines, Trodelvy is also undergoing regulatory review in Singapore.

Reference Source: FDA Approves Trodelvy®, the First Treatment for Metastatic Triple-Negative Breast Cancer Shown to Improve Progression-Free Survival and Overall Survival