To evaluate the efficacy and safety of Serplulimab in combination with Trastuzumab Restuzumab for the neoadjuvant treatment of triple-negative breast cancer, aiming to provide evidence for optimizing the strategy of combining immunotherapy with ADC drugs in the neoadjuvant setting.
This is a prospective, single-arm, open-label, Phase II clinical trial investigating the efficacy and safety of a non-chemotherapy regimen comprising Serplulimab (an anti-PD-1 monoclonal antibody) and Trastuzumab Restuzumab (SHR-A1811, an antibody-drug conjugate) as neoadjuvant therapy for early-stage triple-negative breast cancer. Primary Objective:To assess the pathological complete response rate, defined as the absence of invasive carcinoma in both the breast and sampled regional lymph nodes (ypT0/Tis ypN0), following neoadjuvant treatment with serplulimab plus SHR-A1811. Secondary Objectives: To evaluate invasive disease-free survival, event-free survival, and the objective response rate according to RECIST 1.1 criteria. To determine the rate of breast-conserving surgery. To characterize the safety and tolerability profile of the combination regimen, including the incidence and severity of adverse events. Study Design: This study employs a Simon's two-stage, single-arm design. Approximately 84 treatment-naïve female patients with early-stage TNBC (clinical stage T1cN1-2 or T2-4N0-2) will be enrolled. Participants will receive six cycles of serplulimab and SHR-A1811 prior to definitive surgery. The primary endpoint will be centrally assessed on the surgical pathology specimen. Interventions: Serplulimab: Administered intravenously at a protocol-specified dose every three weeks for six cycles. SHR-A1811: Administered intravenously at a protocol-specified dose every three weeks for six cycles. Statistical Methods: The study is designed to test the hypothesis that the combination regimen will increase the pCR rate from a historical benchmark of 30% to 40%. With a one-sided alpha level of 0.05 and 80% statistical power, a minimum of 75 evaluable patients is required. Allowing for an estimated 10% dropout rate, a total of 84 patients will be enrolled. The primary efficacy analysis of the pCR rate will be conducted on the full analysis set using an exact binomial test. The 95% confidence interval for the pCR rate will be calculated via the Clopper-Pearson exact method. Time-to-event endpoints will be analyzed using the Kaplan-Meier method.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
84
Administered intravenously at a protocol-specified dose, once every 3 weeks (Q3W), for a total of 6 cycles in the neoadjuvant setting.
Administered intravenously at a protocol-specified dose, once every 3 weeks (Q3W), for a total of 6 cycles in the neoadjuvant setting.
the First Affiliated Hospital of the Air Force Medical University
Xi'an, China
Pathological Complete Response (pCR) Rate
Proportion of participants achieving a pathological complete response, defined as the absence of residual invasive cancer in the breast and sampled ipsilateral lymph nodes (ypT0/Tis, ypN0) upon pathological review of the surgical resection specimen following completion of neoadjuvant therapy.
Time frame: At the time of definitive surgery (after 6 cycles of neoadjuvant therapy; each cycle is 21 days).
Objective Response Rate (ORR)
Proportion of participants achieving a best overall response of complete response or partial response, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 during the neoadjuvant treatment phase.
Time frame: From baseline until the end of neoadjuvant therapy (up to 6 cycles), with tumor assessments performed at the end of Cycles 2, 4, and 6（each cycle is 21days).
Invasive Disease-Free Survival (iDFS)
Time from the date of definitive surgery to the date of the first occurrence of invasive ipsilateral breast tumor recurrence, invasive loco-regional recurrence, distant recurrence, or death from any cause.
Time frame: From surgery until first documented iDFS event or death, assessed up to 5 years (60 months).
Event-Free Survival (EFS)
Time from the date of enrollment to the date of the first occurrence of any of the following: disease progression that precludes planned surgery, invasive local/regional or distant recurrence following surgery, or death from any cause.
Time frame: From enrollment until first documented EFS event or death, assessed up to 5 years (60 months).
Breast-Conserving Surgery Rate
Proportion of participants who undergo successful breast-conserving surgery as the definitive surgical procedure following neoadjuvant therapy.
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Time frame: During surgery
Incidence and Severity of Adverse Events
Frequency, severity (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0), and investigator-assessed relationship to study treatment of all adverse events and serious adverse events.
Time frame: From first study treatment administration until 30 days after the last dose (approximately 25 weeks).