to Evaluate Efficacy and Safety of HLX10 in Combination With Chemotherapy Versus Placebo in Combination With Chemotherapy as Neoadjuvant Therapy and HLX10 Versus Placebo as Adjuvant Therapy in Patients With Triple Negative Breast Cancer (TNBC)

Study Overview
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Brief Summary
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This study is a randomized, double-Blind,international multi-Centre, phase III clinical study to evaluate efficacy and safety of HLX10 in combination with chemotherapy versus placebo in combination with chemotherapy as neoadjuvant therapy and HLX10 versus placebo as adjuvant therapy in previously untreated and potentially resectable patients with TNBC and without distant metastasis. Eligible subjects in this study will be randomized to Arm A or Arm B at 2:1 ratio as follows: Arm A (HLX10 arm): HLX10 + chemotherapy (nab-paclitaxel carboplatin) (4 cycles) → HLX10 + chemotherapy (doxorubicin or epirubicin cyclophosphamide) (4 cycles) → surgery → HLX10 (9 cycles) Arm B (placebo arm): Placebo + chemotherapy (nab-paclitaxel carboplatin) (4 cycles) → Placebo + chemotherapy (doxorubicin or epirubicin cyclophosphamide) (4 cycles) → surgery → Placebo (9 cycles) The three stratification factors for randomization include: lymph node metastasis (yes or no), size of primary tumor lesion (T1/T2 or T3/T4), asian population (yes or no).

Official Title
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A Randomized, Double-Blind, International Multi-Centre, Phase III Clinical Study to Evaluate Efficacy and Safety of HLX10 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection) in Combination With Chemotherapy Versus Placebo in Combination With Chemotherapy as Neoadjuvant Therapy and HLX10 Versus Placebo as Adjuvant Therapy in Patients With Triple Negative Breast Cancer (TNBC)

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: HLX10
* Drug: nab-paclitaxel, carboplatin, doxorubicin or epirubicin and cyclophosphamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects histologically diagnosed with previously untreated TNBC (lack of human epidermal growth factor receptor-2 [HER2], estrogen receptor [ER], progesterone receptor expression as determined by the study site). Subjects who are judged as one of the following by the American Joint Committee on Cancer (AJCC) within 4 weeks prior to randomisation: T1c, N1-N2, M0 T2, N0-N2, M0 T3, N0-N2, M0 T4a-c, N0-N2, M0. Major organs are functioning well Participant must keep contraception Exclusion Criteria: Subjects with any other active malignancy within 5 years prior to signing the informed consent form or at the same time. Localised tumours that have been cured such as basal cell carcinoma, squamous-cell skin cancer, superficial bladder carcinoma, and cervical cancer in situ are acceptable. Subjects who have received chemotherapy, targeted therapy, or radiotherapy within 12 months prior to the initial dose of the investigational product. Subjects with a history of severe allergy to any monoclonal antibody or investigational product and its excipient. Pregnant or lactating women. Subjects with a known history of psychotropics abuse or drug abuse Subjects presenting other factors not suitable for participation as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HLX10 + chemotherapy→ HLX10<br>HLX10 + chemotherapy (nab-paclitaxel carboplatin) (4 cycles) → HLX10 + chemotherapy (doxorubicin or epirubicin cyclophosphamide) (4 cycles) → surgery → HLX10 (9 cycles) | Drug: HLX10<br>* HLX10 is an innovative monoclonal antibody targeting PD-1，developed by Shanghai Henlius Biotech, Inc.<br>Drug: nab-paclitaxel, carboplatin, doxorubicin or epirubicin and cyclophosphamide<br>* chemotherapeutics<br>|
| Placebo Comparator: Placebo + chemotherapy→ Placebo<br>Placebo + chemotherapy (nab-paclitaxel carboplatin) (4 cycles) → Placebo + chemotherapy (doxorubicin or epirubicin cyclophosphamide) (4 cycles) → surgery → Placebo (9 cycles) | Drug: nab-paclitaxel, carboplatin, doxorubicin or epirubicin and cyclophosphamide<br>* chemotherapeutics<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor assessment | Pathological complete response (pCR) rate (ypT0/Tis, ypN0) (assessed by central pathology laboratory based on American Joint Committee on Cancer (AJCC) staging system) | up till 5 years after the enroll | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Triple Negative Breast Cancer, Previously Untreated, Potentially Resectable, Without Distant Metastasis