On 7 April 2021, the US Food and Drug Administration (FDA) granted regular approval to sacituzumab govitecan (Trodelvy, Immunomedics Inc.) for patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. 

In April 2020, sacituzumab govitecan received accelerated approval for patients with mTNBC who have received at least two prior therapies for metastatic disease. The following study was the confirmatory study for the accelerated approval. 

Efficacy and safety were evaluated in a multicentre, open-label, randomised study (ASCENT; NCT02574455) conducted in 529 patients with unresectable locally advanced or mTNBC who had relapsed after at least two prior chemotherapies, one of which could be in the neoadjuvant or adjuvant setting, if progression occurred within 12 months. Patients were randomised (1:1) to receive sacituzumab govitecan, 10 mg/kg as an intravenous infusion, on days 1 and 8 of a 21-day (n=267) cycle or physician’s choice of single agent chemotherapy (n=262). 

The primary efficacy endpoint was progression-free survival (PFS) in patients without brain metastases at baseline as measured by a blinded, independent, centralised review assessed using RECIST v1.1 criteria. Additional efficacy endpoints included PFS for the full population (with and without brain metastases) and overall survival (OS). 

Among all randomised patients (with and without brain metastases), median PFS for patients receiving sacituzumab govitecan was 4.8 months (95% confidence interval [CI] 4.1, 5.8) compared with 1.7 months (95% CI 1.5, 2.5) in those  receiving chemotherapy (hazard ratio [HR] 0.43; 95% CI 0.35, 0.54; p < 0.0001). Median OS was 11.8 months (95% CI 10.5, 13.8) and 6.9 months (95% CI 5.9, 7.6) respectively (HR 0.51; 95% CI 0.41, 0.62; p < 0.0001). 

Most common adverse reactions (incidence >25%) in patients receiving sacituzumab govitecan are nausea, neutropenia, diarrhoea, fatigue, alopecia, anaemia, vomiting, constipation, rash, decreased appetite, and abdominal pain.

The recommended sacituzumab govitecan dose is 10 mg/kg once weekly on days 1 and 8 of 21-day treatment cycles until disease progression or unacceptable toxicity.

Full prescribing information for Trodelvy is available here

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies. 

This review used the Real-Time Oncology Review pilot programme, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 6 weeks ahead of the FDA goal date. 

This application was granted priority review and breakthrough designation. 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System. 

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA OCE’s Project Facilitate.