Serplulimab Combined With Trastuzumab Rezetecan as Neoadjuvant Therapy for Triple-Negative Breast Cancer

Official title

Serplulimab Combined With Trastuzumab Rezetecan as Neoadjuvant Therapy for Triple-Negative Breast Cancer: A Phase II Single-Arm Clinical Study

Overview

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

• Drug Serplulimab
  Administered intravenously at a protocol-specified dose, once every 3 weeks (Q3W), for a total of 6 cycles in the neoadjuvant setting.
• Drug SHR-A1811
  Administered intravenously at a protocol-specified dose, once every 3 weeks (Q3W), for a total of 6 cycles in the neoadjuvant setting.

Primary outcome measures

• Pathological Complete Response (pCR) Rate [Time frame: At the time of definitive surgery (after 6 cycles of neoadjuvant therapy; each cycle is 21 days).]

Secondary outcome measures (5)

• Objective Response Rate (ORR) [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 frame: From surgery until first documented iDFS event or death, assessed up to 5 years (60 months).]
• Event-Free Survival (EFS) [Time frame: From enrollment until first documented EFS event or death, assessed up to 5 years (60 months).]
• Breast-Conserving Surgery Rate [Time frame: During surgery]
• Incidence and Severity of Adverse Events [Time frame: From first study treatment administration until 30 days after the last dose (approximately 25 weeks).]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• the First Affiliated Hospital of the Air Force Medical University — Xi'an

Identifiers

NCT: NCT07466303 · KY20252486-F-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗