Clinical trial NCT06394661: Serplulimab Plus Chemotherapy for Early-stage HR+/HER2- Breast Cancer
Official title: Serplulimab Combined With NabPE for Early-stage Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2-) Breast Cancer- A Single-arm, Multicenter, Phase 2 Clinical Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: HR+ breast cancer
neoadjuvant
serplulimab
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2024-05-01
Enrollment: 109
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if serplulimab is effective in early HR+/HER2- breast cancer. It will also learn about the safety of serplulimab. The main questions it aims to answer are:

Does serplulimab combined with neoadjuvant chemotherapy improve the pCR rate of early HR+/HER2- breast cancer? What medical problems do participants have when receiving serplulimab? Researchers will compare the effect of serplulimab combined with chemotherapy to the effect of chemotherapy reported in literature.

Participants will: Receive serplulimab plus chemotherapy every 3 weeks for 6 cycles; All patients will receive surgery, and the primary end point is a pathological complete response at the time of definitive surgery; After definitive surgery, the participants will receive adjuvant serplulimab every 3 weeks for up to 6 months from the beginning of the treatment.

Detailed description: In recent years, significant progress has been made in the immunotherapy of breast cancer, and PD1/PDL1 inhibitors have achieved good results in the treatment of triple-negative breast cancer. There have also been many attempts to apply them in HR+/HER2- breast cancer. In the I-SPY2 study, Pembrolizumab combined with chemotherapy increased the pCR rate of HR+/HER2- breast cancer from 13% in the chemotherapy alone group to 30%. In the KEYNOTE756 study, Pembrolizumab in combination with chemotherapy increased the pCR rate by 8.5% (24.3% vs. 15.6%) compared to the chemotherapy-only arm in HR+/HER2- breast cancer. pCR rates in the Nivolumab arm of the CheckMate 7FL study were 24.5% compared with 13.8% in the control arm. While further long-term follow-up data are still needed to confirm patient benefit, it still provides a new treatment option for HR+/HER2- breast cancer patients.

The neoadjuvant treatment options commonly used for HR+/HER2- breast cancer are mainly anthracycline sequential or combined with paclitaxel chemotherapy regimens. Several clinical studies have confirmed that albumin paclitaxel is more effective than solvent-based paclitaxel, and therefore, albumin paclitaxel in combination with epirubicin has also become a commonly used chemotherapy regimen in clinical practice.

The aim of this study was to explore the efficacy and safety of the Serplulimab combined with nab-paclitaxel and epirubicin in the neoadjuvant treatment of HR+/HER2- breast cancer

Eligibility criteria: Inclusion Criteria

Patients must meet all of the following criteria to be eligible:

Age: ≥18 years old.

Clinical-pathological confirmation:

cT2-cT4 breast cancer, or cT1c with axillary lymph node metastasis.

Histopathologically confirmed HR+/HER2- invasive breast cancer:

ER and/or PR positive (IHC nuclear staining ≥1%).

HER2-negative (IHC 0 or 1+ without FISH testing, or IHC 2+ with FISH-negative amplification).

Ki67 ≥20%.

Clinically measurable lesions:

Measurable lesions confirmed by ultrasound, mammography, or MRI (optional) within 1 month prior to randomization.

Adequate organ and bone marrow function (within 1 month prior to chemotherapy):

Absolute neutrophil count (ANC) ≥2.0 × 10\^9/L.

Hemoglobin ≥90 g/L.

Platelet count ≥100 × 10\^9/L.

Total bilirubin \<1.5 × ULN (upper limit of normal).

Creatinine \<1.5 × ULN.

AST/ALT \<1.5 × ULN.

Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% by echocardiography.

Reproductive status: Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization.

ECOG performance status: ≤1.

Informed consent: Signed written informed consent.

Exclusion Criteria

Patients meeting any of the following criteria will be excluded:

Evidence of metastatic breast cancer:

Prior systemic therapy: Chemotherapy, endocrine therapy, targeted therapy, or radiotherapy for the current breast cancer.

Second primary malignancy, except: Adequately treated non-melanoma skin cancer.

Prior immunotherapy: Treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or other immune checkpoint inhibitors.

Immune-related conditions:

Diagnosed immunodeficiency or active autoimmune disease.

Severe cardiopulmonary disease: Uncontrolled or clinically significant.

Active hepatitis B or C.

Pregnancy or lactation: Pregnant or breastfeeding women.

Other contraindications: Severe uncontrolled comorbidities deemed by investigators to contraindicate chemotherapy or PD-1 inhibitor therapy.

Primary outcomes:
measure: pathological complete response
timeFrame: up to 24 weeks
Secondary outcomes:
measure: Event-Free Survival (EFS)
timeFrame: 5-10 years
measure: DFS
timeFrame: 5-10 years
measure: Objective Response Rate (ORR)
timeFrame: up to 24 weeks
measure: adverse events
timeFrame: After each cycle of chemotherapy (21 days as 1 cycle)]
Other outcomes:
measure: PDL1 expression
timeFrame: up to 24 weeks
measure: next-generation sequencing (NGS)
timeFrame: up to 24 weeks
measure: blood based biomarker
timeFrame: up to 24 weeks
measure: 9-item depression module of the Patient Health Questionnaire-9
timeFrame: up to 24 weeks
Locations:
city: Henan
country: China
facility: Henan cacer hospital
state: Henan
Study officials:
affiliation: Henan Cancer Hospital
name: Zhenzhen Liu, PhD
role: PRINCIPAL_INVESTIGATOR
References: