Advanced Breast Cancer
Conditions
Brief summary
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.
Interventions
DRUGToripalimab
Toripalimab
DRUGTPC
Treatment of Physician's Choice
Sponsors
Henan Cancer Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntary participation: the subject must give written informed consent, be compliant, and agree to attend all follow-up visits. 2. Age ≥ 18 years. 3. ECOG performance-status score ≤ 1 and life expectancy ≥ 3 months. 4. 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). 5. 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: 1. 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). 2. 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. 6. 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). 7. At least one measurable lesion per RECIST v1.1. 8. Adequate organ function, defined as: Haematology (no transfusion within 14 days): 1. Haemoglobin ≥ 9 g/dL 2. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L 3. Platelet count ≥ 100 × 10⁹/L . Serum chemistry: <!-- --> 1. Total bilirubin ≤ 1.5 × ULN, or if total bilirubin \> ULN then direct bilirubin ≤ ULN 2. ALT and AST ≤ 2.5 × ULN 3. Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min 9. 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.
Exclusion criteria
1. Uncontrolled central-nervous-system metastases (symptomatic or requiring corticosteroids or mannitol for symptom control). 2. Clinically significant or uncontrolled cardiac disease within 6 months before first dose, including congestive heart failure, angina, myocardial infarction, or ventricular arrhythmia. 3. Malignancy within 5 years before first dose, except adequately treated basal-cell carcinoma of the skin or carcinoma in situ of the cervix. 4. Active autoimmune disease requiring systemic therapy within 2 years before first dose, except vitiligo, type-1 diabetes, or residual hypothyroidism due to autoimmune thyroiditis managed with hormone replacement only. 5. Uncontrolled pleural, pericardial, or ascitic fluid requiring repeated drainage. 6. Documented human immunodeficiency virus (HIV) infection. 7. Documented hepatitis-B infection or active hepatitis-C infection. 8. Prior hypersensitivity to any component or excipient of the investigational product(s). 9. Any condition judged by the investigator to render the patient unsuitable for trial participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR by investigator | At baseline, at the time point of every 8 weeks within first 24 weeks, thereafter every 12 weeks | ORR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response) or PR (partial response) per RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | up to 3 years | PFS is the time from the date of first dose until the date of objective radiographic disease progression or death (by any cause in the absence of progression). |
| DCR | At baseline, at the time point of every 8 weeks within first 24 weeks, thereafter every 12 weeks | DCR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response), PR (partial response) or SD (stable disease) per RECIST v1.1. |
| DoR | up to 3 years | DoR is the time from the date of first detection of objective response (which is subsequently confirmed) until the date of objective radiographic disease progression. |
| OS | up to 3 years | OS is the time from the date of first dose until the date of death by any cause. |
| Safety (Proportion of AEs) | from time of informed consent provided to 30 days after the last dose of study therapy | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Percentage of participants who experienced an adverse event and discontinued study drug due to an AE. |
Countries
China
Contacts
CONTACTMin Yan, Chief physician
CONTACTMeng wei Zhang, Associate Chief Physician
PRINCIPAL_INVESTIGATORMin Yan, Chief physician
Henan Cancer Hospital
Outcome results
None listed