A Multicohort Study of Toripalimab in Combination With Investigator-Selected Chemotherapy for Advanced HER2-Negative Breast Cancer
To evaluate the efficacy and safety of toripalimab in combination with investigator-selected chemotherapy in patients with recurrent or metastatic HER2-negative breast cancer who have failed prior systemic therapy.
• Voluntary participation: the subject must give written informed consent, be compliant, and agree to attend all follow-up visits.
• Age ≥ 18 years.
• ECOG performance-status score ≤ 1 and life expectancy ≥ 3 months.
• Histologically or cytologically confirmed HER2-negative breast cancer (HER2-negative is defined as either IHC 0, IHC 1+, or IHC 2+ with a negative in-situ-hybridisation \[ISH\] result).
• For subjects with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC):
• \- Must have experienced progression during/after at least one prior systemic regimen for recurrent/metastatic disease (recurrence ≤ 12 months after neoadjuvant/adjuvant therapy counts as first-line failure).
• \- Cohort assignment by prior immune-checkpoint-inhibitor (ICI) exposure:
‣ Cohort A - ICI-pretreated:
⁃ If ICI was given in adjuvant setting, recurrence must occur ≥ 12 months after completion of immunotherapy.
• If ICI was given in neoadjuvant or metastatic setting, best overall response must have met clinical-benefit criteria (PR, CR, or SD \> 24 weeks).
‣ Cohort B - ICI-naïve: no prior anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or any other antibody targeting T-cell co-stimulatory or checkpoint pathways.
• For subjects with hormone-receptor-positive (HR+) breast cancer:
‣ Must have progressed after ≥ 2 prior endocrine regimens in the recurrent/metastatic setting (unless investigator judges no endocrine benefit), and
⁃ Must have progressed after ≥ 1 prior systemic chemotherapy for recurrent/metastatic disease (recurrence ≤ 12 months after adjuvant/neoadjuvant therapy counts as first-line failure).
• At least one measurable lesion per RECIST v1.1.
• Adequate organ function, defined as:
• Haematology (no transfusion within 14 days):
‣ Haemoglobin ≥ 9 g/dL
‣ Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
‣ Platelet count ≥ 100 × 10⁹/L . Serum chemistry:
• <!-- -->
∙ Total bilirubin ≤ 1.5 × ULN, or if total bilirubin \> ULN then direct bilirubin ≤ ULN
‣ ALT and AST ≤ 2.5 × ULN
‣ Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min
• Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days before first dose and must use highly effective contraception from first dose until 6 months after last dose.
‣ WOCBP is defined as any sexually mature female who has not undergone hysterectomy or bilateral oophorectomy and who has not experienced natural amenorrhoea for ≥ 24 consecutive months (including women with treatment-induced amenorrhoea).Men whose partners are WOCBP must also use effective contraception during the same period.