Neoadjuvant Sacituzumab Govitecan plus Pembrolizumab versus Chemotherapy in Clinical Stage II-III Triple-Negative Early Breast Cancer

The primary objective is to evaluate event-free survival at 3 years in clinical stage II-III triple-negative early breast cancer. In cohort II, the study also aims to demonstrate superiority of neoadjuvant sacituzumab govitecan plus pembrolizumab versus standard-of-care chemotherapy with respect to 3-year event-free survival and pathologic complete response, which are clinically relevant measures of treatment efficacy and disease control. Secondary objectives include assessment of clinical response after 12 weeks of neoadjuvant treatment, 3-year distant disease-free survival, relapse-free survival, locoregional relapse-free survival, and overall survival. Health-related quality of life is also evaluated, and toxicity is assessed in cohort II.

The sponsor did not provide the number of participants or a detailed description of the study population. The trial included patients of both sexes with triple-negative breast cancer or TNBC-like disease, aged at least 18 years, with clinical stage II–III, no clinical evidence of distant metastasis, and adequate performance status. Selection was based on histologically confirmed unilateral primary invasive breast carcinoma and completion of 9–12 weeks of neoadjuvant treatment, with additional pathology confirmation and protocol-defined clinical and laboratory requirements. Relevant considerations included the ability to complete quality-of-life questionnaires, willingness and ability to comply with treatment and follow-up, and use of required contraception where applicable. Key exclusion criteria were not fully described in the source.

The study is a Phase III clinical trial in triple-negative breast cancer with neoadjuvant treatment. It compares sacituzumab govitecan plus pembrolizumab with standard-of-care chemotherapy. The overall trial duration is planned from 31 March 2026 to 30 September 2032. Eligible participants are enrolled after screening and baseline assessments, including confirmation of histology, disease stage, performance status, laboratory requirements, ECG, pregnancy testing when applicable, and central pathology review of the tumour block. Study treatment is then administered according to the assigned regimen, with follow-up assessments performed at protocol-defined timepoints to evaluate efficacy, safety, clinical response, and quality of life. The end-of-study visit is performed at the end of the protocol-defined observation period. Participant involvement is expected to continue from screening through treatment and follow-up for the full study period applicable to the individual participant. Early termination may occur in the event of disease progression, unacceptable toxicity, withdrawal of consent, non-compliance with protocol requirements, or other medical reasons that prevent further study treatment or follow-up.

The investigational treatment included sacituzumab govitecan, supplied as Trodelvy 200 mg powder for concentrate for solution for infusion, and administered by intravenous infusion at a dose of 10 mg/kg. The study also included pembrolizumab, supplied as KEYTRUDA 25 mg/mL concentrate for solution for infusion, and administered by intravenous infusion at a dose of 200 mg. Both agents were used as test treatments in the trial.

The non-experimental treatment was standard-of-care chemotherapy, used as the comparator treatment. The source data do not provide further details on dosing schedules, administration intervals, or compliance monitoring.

Efficacy will be assessed using event-free survival after 36 months as a primary endpoint. In cohort I, this is defined as time from registration to any invasive breast cancer event, death, or secondary malignancy, according to STEEP 2.0 criteria. In cohort II, it is defined as time from registration to any invasive breast cancer event, death, secondary malignancy, or local progress precluding surgery in neoadjuvant treated patients. In cohort II, pathological complete response is also a primary efficacy endpoint and is defined as no invasive disease in breast and lymph nodes (ypT0/is, ypN0) in patients of both arms.

Secondary efficacy assessments include clinical response measured by palpation, ultrasound, mammography, or MRI. Additional efficacy endpoints include overall survival, 3-year distant disease-free survival, 3-year recurrence-free survival, and 3-year locoregional recurrence-free survival, each as defined in STEEP 2.0. Change in health-related quality of life is also assessed between baseline, after completion of standard-of-care neoadjuvant treatment, and at following defined timepoints.