A Phase 3 Randomized Study of Sacituzumab Govitecan and Pembrolizumab Versus Physician's Choice in Triple Negative Breast Cancer with Residual Invasive Disease

The primary objective of this study is to compare **invasive disease-free survival (iDFS)** between the combination of sacituzumab govitecan and pembrolizumab versus the treatment of physician's choice in patients with **Triple Negative Breast Cancer** who have residual invasive disease following surgery and neoadjuvant therapy. This objective is clinically relevant as it aims to evaluate the efficacy of the investigational treatment in preventing the recurrence of invasive disease, which is a critical outcome for improving long-term patient prognosis.

Secondary objectives include:

• Comparing overall survival (OS) between the two treatment arms, which is essential for assessing the ultimate benefit of the treatment in extending life expectancy.
• Comparing distant disease-free survival (dDFS) as assessed by investigators, which provides insights into the treatment's effectiveness in preventing metastasis.
• Comparing recurrence-free survival (RFS) as assessed by investigators, which evaluates the treatment's ability to prevent any form of cancer recurrence.
• Comparing safety and tolerability between the two arms, which is crucial for understanding the risk-benefit profile of the treatment.
• Comparing time to worsening (TTW) of quality of life (QoL) outcomes as measured by the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B), which assesses the impact of treatment on patients' quality of life.

The clinical trial involves a total of **1059 participants** diagnosed with **Triple Negative Breast Cancer** (TNBC). The study population is exclusively female, with an age range of 18 years and older. Participants were selected based on specific criteria, including a confirmed diagnosis of TNBC with residual invasive disease post-neoadjuvant therapy and surgery, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. The trial does not include male subjects. Participants must have undergone appropriate surgical and radiotherapy procedures and demonstrated adequate hepatic function. The trial population includes individuals who are considered vulnerable, as defined by the study's criteria. Lifestyle factors such as diet and physical activity are not specified in the available data. The selection process ensures that participants have received prior neoadjuvant chemotherapy and, if applicable, adjuvant pembrolizumab treatment. The study aims to compare invasive disease-free survival between SG and pembrolizumab versus TPC.

The clinical trial is designed as a **randomized**, open-label, Phase 3 study to evaluate the efficacy of adjuvant **sacituzumab govitecan** and **pembrolizumab** compared to the treatment of physician's choice in patients with **triple negative breast cancer** who have residual invasive disease following surgery and neoadjuvant therapy. The primary objective is to compare invasive disease-free survival (iDFS) between the two treatment groups. The trial is expected to commence recruitment on October 1, 2024, and is estimated to conclude by May 20, 2033.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, performance status, and prior treatment history. The inclusion criteria require patients to be 18 years or older, with a history of specific clinical stages of TNBC, and to have completed neoadjuvant chemotherapy. The screening visit will also ensure the absence of distant metastatic disease and confirm adequate surgical and radiotherapy interventions.

Following the screening, participants will be randomized to receive either the investigational treatment or the physician's choice of therapy. The investigational treatment involves the administration of **sacituzumab govitecan** via **intravenous infusion** and **pembrolizumab** also via **intravenous infusion**. The treatment period is structured in cycles, with a maximum treatment period of 21 days per cycle. Participants will be monitored through regular follow-up visits to assess treatment efficacy and safety, including the incidence of treatment-emergent adverse events (TEAEs) and clinical laboratory abnormalities.

The end-of-study visit will occur after the completion of the treatment cycles or upon early termination. Conditions that may lead to early termination from the study include the occurrence of unacceptable toxicity, disease progression, or withdrawal of consent by the participant. The expected length of participant involvement will vary depending on individual response to treatment and adherence to the study protocol.

The clinical trial involves the administration of **Xeloda** 500 mg film-coated tablets, which contain the active substance **capecitabine**. This medication is a non-cytotoxic fluoropyrimidine carbamate, functioning as an orally administered precursor. The pharmaceutical form is a film-coated tablet, and the route of administration is oral. The dosage is calculated based on body surface area, with a maximum daily dose of 1000 mg/m² and a total maximum dose of 28000 mg/m² over a treatment period of 21 days. Compliance with the dosing schedule is monitored through regular assessments.

**Trodelvy** 200 mg powder for concentrate for solution for infusion is another treatment used in the trial. The active substance is **sacituzumab govitecan**, an antibody-drug conjugate. The pharmaceutical form is a powder for concentrate, which is reconstituted for intravenous infusion. The dosage is determined by body weight, with a maximum daily dose of 10 mg/kg and a total maximum dose of 160 mg/kg over a 21-day treatment period. The administration is conducted under controlled conditions to ensure participant safety and adherence to the protocol.

**KEYTRUDA** 25 mg/mL concentrate for solution for infusion is also utilized in the study. The active substance, **pembrolizumab**, is a humanized monoclonal anti-programmed cell death-1 (PD-1) antibody. The pharmaceutical form is a concentrate for solution, administered via intravenous infusion. The maximum daily dose is 200 mg, with a total maximum dose of 1600 mg over a 21-day treatment period. The administration is performed in a clinical setting, with careful monitoring to ensure compliance and manage any potential adverse effects.

Efficacy in the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is **invasive disease-free survival (iDFS)**, defined as the time from the date of randomization to death from any cause or the occurrence of invasive local, regional, or distant recurrence, or invasive contralateral breast cancer. Secondary endpoints include overall survival (OS), distant disease-free survival (dDFS), recurrence-free survival (RFS), incidence of treatment-emergent adverse events (TEAEs) and clinical laboratory abnormalities, and time to worsening (TTW) of quality of life based on the FACT-B Trial Outcome Index (TOI) score.

The trial will compare the efficacy of sacituzumab govitecan and pembrolizumab versus treatment of physician’s choice in patients with triple-negative breast cancer who have residual invasive disease after surgery and neoadjuvant therapy. The efficacy parameters will be measured and collected at specified timepoints throughout the study duration, with the primary focus on the time from randomization to the occurrence of the defined events for each endpoint. The analysis will involve statistical methods appropriate for time-to-event data to evaluate the differences between the treatment groups.