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

NCT07466303 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: KY20252486-F-1
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Serplulimab Combined With SHR-A1811 as Neoadjuvant Therapy for Triple-Negative Breast Cancer

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

Outcome Measures

Primary Outcomes (1)

• 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.

  At the time of definitive surgery (after 6 cycles of neoadjuvant therapy; each cycle is 21 days).

Secondary Outcomes (5)

• 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).

• Invasive Disease-Free Survival (iDFS)

  From surgery until first documented iDFS event or death, assessed up to 5 years (60 months).

• Event-Free Survival (EFS)

  From enrollment until first documented EFS event or death, assessed up to 5 years (60 months).

• Breast-Conserving Surgery Rate

  During surgery

• Incidence and Severity of Adverse Events

  From first study treatment administration until 30 days after the last dose (approximately 25 weeks).

Study Arms (1)

Neoadjuvant Serplulimab + SHR-A1811

EXPERIMENTAL

All enrolled participants will receive the investigational combination therapy as neoadjuvant treatment. This regimen consists of Serplulimab (an anti-PD-1 monoclonal antibody) and SHR-A1811 (Trastuzumab Restuzumab , an antibody-drug conjugate). Both agents are administered intravenously every 3 weeks (Q3W) for 6 cycles prior to definitive surgery. The primary objective is to evaluate the efficacy and safety of this chemotherapy-free combination in patients with early-stage triple-negative breast cancer (TNBC).

Drug: Serplulimab; Drug: SHR-A1811

Interventions

Serplulimab DRUG

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

Neoadjuvant Serplulimab + SHR-A1811

SHR-A1811 DRUG

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

Neoadjuvant Serplulimab + SHR-A1811

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xijing Hospital: lead

Study Sites (1)

the First Affiliated Hospital of the Air Force Medical University

Xi'an, 710032, China

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Ju Liang Zhang, Prof

CONTACT

029-84775271; vascularzhang@163.com

Mei Ling Huang, MD

CONTACT

029-84775271; huangmeiling@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2026
• First Posted: March 12, 2026
• Study Start: March 25, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): April 1, 2031
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

CN (1)