Breast Cancer, Serplulimab Combined With SHR-A1811 as Neoadjuvant Therapy for Triple-Negative Breast Cancer
Conditions
Keywords
Neoadjuvant Therapy, Pathological Complete Response, Serplulimab, PD-1 Inhibitor, Antibody-Drug Conjugate, Trastuzumab Deruxtecan, Phase II Clinical Trial, Triple-Negative Breast Cancer, HER2-Low Breast Cancer
Brief summary
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.
Detailed description
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.
Interventions
DRUGSerplulimab
Administered intravenously at a protocol-specified dose, once every 3 weeks (Q3W), for a total of 6 cycles in the neoadjuvant setting.
DRUGSHR-A1811
Administered intravenously at a protocol-specified dose, once every 3 weeks (Q3W), for a total of 6 cycles in the neoadjuvant setting.
Sponsors
Xijing Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Female patients aged 18 to 70 years, inclusive. * Histologically confirmed, treatment-naïve, early-stage triple-negative breast cancer (TNBC), defined as estrogen receptor (ER) and progesterone receptor (PR) expression \<1% by immunohistochemistry (IHC), and human epidermal growth factor receptor 2 (HER2)-negative (IHC 0/1+ or IHC 2+ with negative in situ hybridization confirmation) per current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. * Clinical stage T1cN1-2 or T2-4N0-2 according to the American Joint Committee on Cancer (AJCC) staging system, 8th edition. * At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate hematologic, hepatic, renal, and cardiac function within 14 days prior to enrollment: * Hematologic: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥90 g/L (without transfusion or growth factor support within 14 days). * Hepatic: Total bilirubin ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN. * Renal: Serum creatinine and blood urea nitrogen (BUN) ≤1.5 × ULN. * Cardiac: Left ventricular ejection fraction (LVEF) ≥50% measured by echocardiogram; corrected QT interval (QTc) \<470 ms on 12-lead electrocardiogram (ECG). * Willingness to provide archival or fresh tumor tissue sample for programmed death-ligand 1 (PD-L1) biomarker analysis using the 22C3 pharmDx assay. * Ability to understand and willingness to sign a written informed consent document.
Exclusion criteria
* Evidence of metastatic (Stage IV) disease or bilateral breast cancer at diagnosis. * Prior systemic anticancer therapy (including chemotherapy, endocrine therapy, immunotherapy, or biological therapy) for any malignancy within 4 weeks before the first dose of study treatment. * Diagnosis of any other malignancy within the past 5 years, except for adequately treated non-melanoma skin cancer, basal cell carcinoma, or carcinoma in situ of the cervix. * Known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV-DNA ≥500 IU/mL), or hepatitis C virus (detectable HCV-RNA). * Active autoimmune disease requiring systemic immunosuppressive therapy within the past 2 years. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic antibiotic therapy within 2 weeks, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements. * History of allogeneic hematopoietic stem cell or solid organ transplantation. * Pregnant or lactating women, or women of childbearing potential who are unwilling to use a highly effective method of contraception during the treatment period and for at least 7 months after the last dose. * Known hypersensitivity to any component of serplulimab or SHR-A1811. * Any condition that, in the opinion of the investigator, would compromise patient safety or interfere with the completion of the study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | At the time of definitive surgery (after 6 cycles of neoadjuvant therapy; each cycle is 21 days). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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). | 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. |
| Invasive Disease-Free Survival (iDFS) | From surgery until first documented iDFS event or death, assessed up to 5 years (60 months). | 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. |
| Event-Free Survival (EFS) | From enrollment until first documented EFS event or death, assessed up to 5 years (60 months). | 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. |
| Breast-Conserving Surgery Rate | During surgery | Proportion of participants who undergo successful breast-conserving surgery as the definitive surgical procedure following neoadjuvant therapy. |
| Incidence and Severity of Adverse Events | From first study treatment administration until 30 days after the last dose (approximately 25 weeks). | 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. |
Countries
China
Contacts
CONTACTJu Liang Zhang, Prof
CONTACTMei Ling Huang, MD
Outcome results
None listed