A Trial of Camrelizumab Plus Nab-paclitaxel and Levocetirizine in Metastatic or Recurrent TNBC

Camrelizumab Plus Nab-paclitaxel and Anti-histamine Drug Levocetirizine in Metastatic or Recurrent Triple-negative Breast Cancer: a Randomized, Double-arm, Phase 2 Randomized Controlled Trial

This is a phase II, explorative, open-labeled, multi-centered, double-arm, investigator-initiated clinical trial of Camrelizumab (an anti-PD-1 antibody) in combination with Nab-paclitaxel (a chemotherapeutic agent against breast cancer) and Levocetirizine (an antihistamine) in patients with advanced triple-negative breast cancer. 60 subjects will be enrolled in multiple centers. This study aims to evaluate the effects of Camrelizumab combined with Nab-paclitaxel and Levocetirizine in the treatment of advanced TNBC.

This is a phase II, explorative, open-labeled, multi-centered, double-arm, investigator-initiated clinical trial to evaluate the effects of Camrelizumab combined with Nab-paclitaxel and Levocetirizine in the treatment of advanced TNBC. The study aims to enroll 60 subjects in multiple centers. The primary objective is to assess the overall response rate (ORR). All enrolled patients will be treated with Camrelizumab 200mg (iv. 3mg/kg for patient whose weight is below 50kg) on day 1 of each 3 week, and Nab-paclitaxel 100mg/m2, iv, on d1,8,15 of each 4 week, in combination with Levocetirizine of 5mg, po., 3 days before 1st administration.

Inclusion Criteria:

1. Sign the written informed consent;

2. Aged ≥ 18 and ≤ 70 years old;

3. Confirmed recurrent and metastatic triple negative breast cancer by imaging and pathology (ER negative (IHC ER positive percentage < 1%), PR negative (IHC PR positive percentage < 1%), HER2 negative (IHC -/+or IHC++but FISH/CISH -)), at least one measurable focus meeting the RECIST v1.1 standard;

4. Untreated local recurrence of unresectable TNBC or untreated distant metastasis of TNBC

5. Must be able to swallow tablets;

6. Clarify the positive status of PD-L1 expression and CPS score ≥ 1

7. ECOG score: 0 to 1;

8. Expected survival period ≥ 12 weeks;

9. The results of patient's blood tests are as follows (excluding the use of any blood components and cell growth factors during screening):

   • Absolute neutrophil count ≥ 1.5 × 109/L;
   • Platelets ≥ 100 × 109/L;
   • Hemoglobin ≥ 9g/dL;
   • Serum albumin ≥ 3g/dL;
   • Thyroid stimulating hormone (TSH) ≤ ULN (if abnormal, T3 and T4 levels should be examined simultaneously. If T3 and T4 levels are normal, they can be included in the group);
   • Bilirubin ≤ 1.0 times ULN (Gilbert's syndrome or liver metastasis subject total bilirubin ≤ 1.5 times ULN);
   • ALT and AST ≤ 1.5 times ULN (liver metastasis subjects ≤ 3 times ULN);
   • AKP ≤ 2.5 times ULN;
   • Renal function within 7 days before the first administration: serum creatinine ≤ 1.5 times ULN or creatinine clearance rate ≥ 60mL/min (using the standard Cockcroft Gault formula, see Appendix 3);

10. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose and must be willing to use very efficient barrier methods of contraception for the course of the study through 6 months after the last dose of study treatment.

11. Left ventricular ejection fraction ≥ 50%

Exclusion Criteria:

1. Received other interventional clinical trials within 28 days before the first dose;

2. Failure to recover from adverse reactions of previous treatment

3. Neurological disorders of grade ≥ 2

4. Untreated active brain metastases or meningeal metastases

5. Previously received nab-paclitaxel neoadjuvant therapy or adjuvant therapy and experienced local recurrence or distant metastasis within 12 months;

6. Has experienced severe allergic reactions to other monoclonal antibodies;

7. Received other anti-tumor treatments within 28 days before the first administration;

8. Suffering from hypertension and unable to achieve good control with antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);

9. Received antibody or T cell co stimulatory therapy such as PD-1, PD-L1, PD-L2, CTLA-4, Tim3, LAG3, etc;

10. Special genetic diseases (including rare galactose intolerance, primary lactase deficiency, or glucose galactose malabsorption);

11. Active autoimmune disease or history of autoimmune disease (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or complete remission of childhood asthma without any intervention in adulthood may be included; subjects with asthma requiring medical intervention with bronchodilators may not be included);

12. Heart diseases, such as:

    • NYHA grade 2 or above heart failure
    • Unstable angina pectoris
    • Have experienced a myocardial infarction within the past year
    • Clinically significant supraventricular or ventricular arrhythmias require treatment or intervention；

13. Urine protein level is ≥++, or the 24-hour urine protein level is ≥ 1.0 g;

14. Known genetic or acquired bleeding and thrombophilia tendencies (such as hemophilia patients, coagulation dysfunction, thrombocytopenia, splenomegaly, etc.);

15. Have a history of tuberculosis;

16. Active period of HBV or HCV, and other active infectious diseases;

17. Had or is currently experiencing qualitative pneumonia or requires steroid treatment for pneumonia;

18. Congenital or acquired immune dysfunction (such as HIV infected individuals);

19. Received or about to receive a live vaccine within 4 weeks prior to the study or possibly during the study period;

20. Allergic or contraindicated to the experimental drug.