It has been proved that the achievement of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved outcome across all breast cancer (BC) subtypes. At present, anthracycline and taxanes based chemotherapy is usually the first choice of neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2) negative breast cancer, and the response rate can be more than 2/3. However, there are still some patients not getting satisfactory outcome using this regimen, for whom there is no unified ideal second-line neoadjuvant therapy to choose. Studies on metastatic BC have shown that vinorelbine combined with cisplatin has good efficacy and safety in the treatment of patients after failure or progression with anthracycline and/or taxanes. In other studies, patients with poor response to anthracycline and taxanes based NACT changed to NACT containing vinorelbine could obtain improved long-term survival. These results suggest that adjusting the neoadjuvant therapy according to the efficacy may bring more benefits to patients and vinorelbine combined with cisplatin is one of the second-line options for HER2 negative breast cancer who has been treated by the anthracycline and taxanes based NACT but not getting good efficacy.

Immunotherapy has achieved good efficacy in many malignant tumors. The US Food and Drug Administration (FDA) has approved the indications for the use of pembrolizumab ( an anti-PD-1 antibody) and atezolizumab (an anti -PD-L1 antibody) in patients with unresectable locally advanced or metastatic triple negative breast cancer. In neoadjuvant therapy, many studies have shown that the increase of pCR rate after NACT combined with immunotherapy, and the clinical benefit is obvious in the early stage. This was hypothesized that chemotherapy including anthracyclines or other drugs may have a certain immune activation effect, thus combination of immunotherapy and chemotherapy has significant clinical value in neoadjuvant and adjuvant treatment of breast cancer.

Based on the above background, we propose the hypothesis that camrelizumab combined with vinorelbine and cisplatin can be recommended for HER2 negative breast cancer patients who did not achieve significant efficacy after 2 cycle treatments of anthracycline plus taxanes as first-line neoadjuvant therapy. In order to confirm this hypothesis, we designed the following one centre single arm phase 2 clinical trial.

We defined the target population of our study as those early-stage HER2 negative breast cancer (triple negative breast cancer and HER2 negative hormone receptor positive breast cancer) patients with indications of NACT who did not receive partial response after 2 cycle of standard anthracycline and taxanes treaments according to RECIST 1.1 criteria. We expect to recruit 30 subjects. The enrolled patients will receive 6 cycles of neoadjuvant therapy of camrelizumab combined with vinorelbine and cisplatin (NP) as second-line neoadjuvant therapy. After the patients complete the neoadjuvant therapy or stop treatment due to disease progression, intolerance of adverse reactions or other conditions that the researchers thought they could not continue to benefit from the treatment, they need to undergo surgery in 4 weeks. The subjects have to continue camrelizumab every 3 weeks like during the preoperative phase until it is totally used for 1 year (about 17 cycles in all). In addition, the patients will routinely receive conventional treatment, endocrine therapy and other adjuvant therapy. Our primary objection is to evaluate the efficacy of second-line neoadjuvant therapy with camrelizumab combined with NP; and the secondary objection is to verify this regimen's security. The efficacy of camrelizumab and NP neoadjuvant therapy will be evaluated according to the assessment during treatment, postoperative pathological results and follow-up results. We will record the clinical response, pCR, progression-free survival and overall survival etc. Safety information will be collected continuously at the beginning of study treatment until the completion of follow-up after study treatment. Besides, we will do some exploratory research using the histological or blood samples of the subjects about biomarkers (like tumor infiltrating lymphocytes, expression of PD-L1 etc.) that may be used for clinical prediction, selection of suitable population and other situations.