Clinical Summary: 

• Design/Population: The phase 2 SATEEN trial evaluated sacituzumab govitecan plus trastuzumab in patients with heavily pretreated HER2-positive metastatic breast cancer previously treated with T-DXd.
• Key Outcomes: The combination did not meet the primary end point, with low response rates, limited clinical benefit, and short progression-free survival. Treatment was associated with notable hematologic toxicity.
• Clinical Relevance: Sequential use of TOPO1 inhibitor–based ADCs may have limited efficacy after T-DXd, underscoring the need for alternative therapeutic strategies in this setting.

According to results from the phase 2 SATEEN trial, sacituzumab govitecan plus trastuzumab demonstrated limited clinical activity among patients with HER2-positive metastatic breast cancer previously treated with trastuzumab deruxtecan (T-DXd). 

These results were presented by Paolo Tarantino, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, at the 2026 European Society for Medical Oncology (ESMO) Breast Cancer Congress in Berlin, Germany.

In this single-arm trial, 27 patients received 10mg/kg of sacituzumab govitecan (on days 1 and 8) plus trastuzumab in 21-day cycles until disease progression or unacceptable toxicity. The primary end point was objective-response rate (ORR). Key secondary end points included clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety. 

At analysis, the ORR was 3.7% and the trial was stopped after the first stage. The 18-week clinical benefit rate was 14.8%, median PFS was 2.3 months, and median OS was 9.2 months. The most frequently reported grade ≥3 treatment-related adverse events included neutropenia (59%), anemia (26%), and diarrhea (19%). Treatment-related neutropenic sepsis with multi-organ failure led to 1 death, after which mandatory growth factor support was implemented.

“In heavily pretreated [HER2-positive metastatic breast cancer] after prior T-DXd, [sacituzumab govitecan] plus trastuzumab did not show clinically relevant activity,” concluded Dr Tarantino. “These prospective findings inform the activity of sequential TOPO1 inhibitor–based ADCs in [HER2-positive metastatic breast cancer] and highlight the need for alternative strategies to optimize patients’ outcomes.”

Source: 

Tarantino P. Efficacy and safety of sacituzumab govitecan (SG) plus trastuzumab in patients with HER2+ metastatic breast cancer after prior trastuzumab deruxtecan (T-DXd): Results from the phase II SATEEN trial. Presented at European Society for Medical Oncology (ESMO) Breast Cancer Congress; March 6 - 8, 2026; Berlin, Germany. LBA4.