A Randomized, Double-blind, Placebo-controlled, Phase III Study to Evaluate the Efficacy and Safety of Camrelizumab and Capecitabine Versus Capecitabine as Adjuvant Therapy in Early-stage Triple-negative Breast Cancer Patients With Tertiary Lymphoid Structure in Tumor Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Neoadjuvant Chemotherapy.
This study aims to evaluate the efficacy and safety of camrelizumab in combination with capecitabine compared to placebo in combination with capecitabine as adjuvant therapy for patients with triple-negative breast cancer (TNBC) who have not achieved pathological complete response (pCR) after neoadjuvant chemotherapy and have tertiary lymphoid structures (TLS) in the tumor tissue. The primary endpoint of this study is disease-free survival (DFS) to assess the long-term effectiveness of the treatment. Secondary endpoints include invasive disease- free survival (IDFS), overall survival (OS), distant recurrence-free interval (DRFI), as well as safety and patient-reported outcomes. These endpoints will comprehensively evaluate the effectiveness of the treatment and the overall survival status of the patients. The study anticipates a total sample size of 375 patients, who will be randomly assigned to either the experimental group or the control group. The experimental group will receive 8 cycles of adjuvant therapy of capecitabine and camrelizumab. The control group will receive 8 cycles of adjuvant therapy with capecitabine and placebo. This study aims to investigate whether non-pcr breast cancer patients with TLS in tumors can benefit from the adjuvant immunotherapy.
• Signed informed consent form.
• Female patients aged ≥18 years at the time of signing informed consent.
• Patients with adequate cognitive ability and willingness to understand and comply with the treatment and follow-up plans as required by the study protocol.
• Confirmed invasive breast cancer on histological examination.
• Clinical stage at presentation: cT4/any N/M0, any cT/N2-3/M0, or cT1-3/N0-1/M0 (patients with cT1mi/T1a/T1b/N0 are not eligible).
• Confirmation of TNBC diagnosis and TLS and PD-L1 status through central examination of representative tumor tissue specimens resected during surgery.
• Patients with synchronous bilateral invasive disease or multicentric tumors (involving more than one quadrant) are eligible for the study, provided that all discrete lesions are confirmed by the central laboratory as TNBC and TLS-positive. For patients with multifocal tumors (more than one mass involving the same quadrant), sampling must be performed on at least one lesion, confirmed by the central laboratory as TNBC and TLS-positive.
• For patients with multifocal or multicentric breast cancer, measurement of the largest lesion to determine the T stage is required.
• Confirmation of TNBC and prospective assessment of TLS presence in tumor tissue before study enrollment, confirmed by HE staining and immunofluorescence staining. TLS positivity is defined as the presence of CD3+ and CD20+ cell aggregates identified by HE staining or immunofluorescence staining on tumor tissue or peritumoral tissue sections.
• Completion of preoperative systemic chemotherapy and camrelizumab treatment.
• Pathological assessment after neoadjuvant treatment did not achieve pCR.
• Adequate resection: Complete removal of all clinically evident lesions in the breast and lymph nodes.
• Interval between the date of initial surgery and randomization date not exceeding 12 weeks.
• Eastern Cooperative Oncology Group performance status score of 0 or 1.
• Completion of neoadjuvant therapy with echocardiography or multi-gated acquisition scan showing left ventricular ejection fraction (LVEF) ≥50% during the screening period and an absolute decrease in LVEF compared to pre-chemotherapy LVEF not exceeding 15%. Alternatively, if LVEF assessment was not performed pre-chemotherapy, LVEF must be ≥55% during the screening period post-neoadjuvant therapy.
• Life expectancy ≥6 months.
• Adequate hematological and organ function.
• Negative HIV test result during screening, with the following exceptions: patients with positive HIV test results during screening are eligible to participate in the study, provided they receive stable antiretroviral therapy, have a CD4 count ≥200/µL, undetectable viral load, and no history of AIDS-defining opportunistic infections within 12 months prior to randomization. Investigators should consider potential drug interactions between study treatment and antiretroviral therapy before patient enrollment.
• Negative hepatitis B surface antigen (HBsAg) test result during screening.
• Negative hepatitis C virus (HCV) antibody test result during screening, or positive HCV antibody test result during screening, followed by negative HCV RNA test result.
• For women of childbearing potential: agreement to practice abstinence (no heterosexual intercourse) or use contraception, and agreement not to donate eggs.