Neoadjuvant Camrelizumab Plus Chemotherapy in Triple Negative Breast Cancer

A Phase Ⅱ Study to Evaluate the Efficacy and Safety of Camrelizumab Plus Chemotherapy as Neoadjuvant Therapy With Triple Negative Breast Cancer (TNBC)

The purpose of this study is to evaluate the efficacy and safety of Camrelizumab plus chemotherapy as neoadjuvant therapy and Camrelizumab as adjuvant therapy in participants who have triple negative breast cancer (TNBC).

After a screening phase of approximately 28 days, each participant will receive neoadjuvant study treatment (camrelizumab + chemotherapy) for approximately 24 weeks (8 cycles). Each participant will then undergo definitive surgery 2-4 weeks after the last cycle of the neoadjuvant treatment. After definitive surgery, each participant will receive adjuvant study treatment (camrelizumab) for approximately 27 weeks (9 cycles). Following adjuvant study treatment, each participant will be monitored for safety, survival and disease recurrence.

The primary study hypothesis is that camrelizumab is superior to chemotherapy, in combination with chemotherapy, as measured by the rate of Pathological Complete Response (pCR), Event-free Survival (EFS) and Objective Overall Response Rate (ORR) in participants with TNBC.

Inclusion Criteria:

1. 18-70 Years, female;

2. Histologically documented Triple Negative Breast Cancer (TNBC) patients;

3. The subtypes of TNBC patients should include basal cell-like subtypes (BL1, BL2), Luminal androgenic type (LAR), and other types, such as mesenchymal type (M), mesenchymal stem cell type (MSL) and immunomodulatory type (IM);

4. Previously untreated non-metastatic (M0) TNBC, the primary tumor (T) and regional lymph node (N) combined staging determined by the investigator based on radiological and/or clinical evaluation. Stage at presentation: T1c, N1-N2; T2, N0-N2; T3, N0-N2;

5. Promising radical surgical treatment;

6. At least one measurable lesion according to RECIST 1.1;

7. Life expectancy is not less than 3 months;

8. ECOG: 0～1;

9. Adequate function of major organs meets the following requirements:

   Neutrophils ≥ 1.5×10^9/L Hemoglobin ≥ 90g/L Platelets ≥ 100×10^9/L Total bilirubin≤ 1.5 × the upper limit of normal (ULN) ALT and AST ≤ 2.5 × ULN Serum creatinine ≤1.5 × ULN, Endogenous creatinine clearance ≥50mL/min;

10. Left ventricular ejection fraction (LVEF) ≥50% or ≥ limit of normal (LLN) was evaluated by echocardiography (ECHO) or Multigated Acquisition (MUGA);

11. Women with childbearing potential who are must agree to take effective contraceptive measures during the study period and ≥120 days after the last administration of the study drug, and must have a negative serum pregnancy test result within 7 days prior to initiation of study drug.

12. The patient voluntarily joined the study, signed an informed consent form, had good compliance, and cooperated with follow-up;

Exclusion Criteria:

1. Has participated in an interventional clinical study with an investigational compound within 4 weeks prior to initiation of study treatment;
2. Prior treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies;
3. Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer;
4. Active or history of autoimmune disease or immune deficiency diseases except history of autoimmune-related hypothyroidism, controlled Type 1 diabetes mellitus;;
5. Has a history of (non-infectious) pneumonitis, interstitial lung disease or uncontrollable systematicness diseases, including pulmonary fibrosis, acute lung disease, etc.;
6. Administration of a live attenuated vaccine within 30 days prior to initiation of study treatment or anticipation of need for such a vaccine during the study;
7. Has active infection (CTCAE≥2) needed the treatment of antibiotic within 2 weeks prior to initiation of study treatment;
8. Has a history of serious cardiovascular disease, including myocardial infarction, acute coronary syndrome or coronary angioplasty/stent implantation/bypass grafting history in the past 6 months, and have level II-IV congestion Heart failure (CHF), or III NYHA and IV CHF history;
9. Prior allogeneic stem cell or solid organ transplantation
10. History of neurological or psychiatric disorders, including schizophrenia, severe depressive disorder, bipolar disorder, etc.;
11. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first administration of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
12. History of severe hypersensitivity reactions to other monoclonal antibodies, or intravenous infusion, or Doxorubicin, or cyclophosphamide, or docetaxel;
13. Female patients during pregnancy and lactation, fertile women with positive baseline pregnancy tests or women of childbearing age who are unwilling to take effective contraceptive measures throughout the trial;
14. Any other situation evaluated by researchers.