TNBC - Triple-Negative Breast Cancer
Conditions
Keywords
Immunotherapy, PD-1, CCR8, Triple-Negative Breast Cancer, TNBC
Brief summary
To evaluate the efficacy and safety of LM108 plus toripalimab plusnab-paclitaxel or eribulin as first-line or post-line treatment in patients with metastatic triple-negative breast cancer.
Interventions
DRUGLM-108
LM-108, 10mg/kg, d1, q6w
DRUGToripalimab
Toripalimab, 240 mg, d1, q3w
DRUGEribulin
Eribulin 1.4 mg/m2, d1, 8 , q3w
DRUGNab paclitaxel
Nab paclitaxel 125 mg/m2, d1, 8 , q3w
Sponsors
Fudan University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years old (including boundary value), no gender limit; 2. ECOG score 0-1; 3. Expected survival ≥3 months; 4. Unresectable or metastatic or postoperative recurrent, histologically confirmed advanced triple-negative breast cancer. Triple-negative breast cancer is defined as: ER, PR and HER2 are negative. ER-negative and PR-negative are defined as tumors without positive staining, the proportion of cells in all tumor cells is \<1%; HER2-negative is defined as: HER2 (0), HER2 (1+) or HER2 (2+) detected by immunohistochemistry but negative by fluorescence in situ hybridization (FISH); Cohort 2 requires histological confirmation of PD-L1 CPS ≥ 1; 5. Cohort 1 : at least one prior line at recurrence or metastasis setting with disease progression or intolerable toxicity. In this situation, patients are allowed to be enrolled: the time between the last intravenous dose of adjuvant chemotherapy and first recurrence or metastasis is ≤6 months. Cohort 2: no prior line at recurrence or metastasis setting is allowed, the time between the last intravenous dose of adjuvant chemotherapy and first recurrence or metastasis ≥12 months.; 6. Provide sufficient fresh tissue specimens for biomarker analysis before treatment; 7. According to RECISTv1.1 standard, there is at least 1 measurable lesion; 8. Appropriate bone marrow and organ function before first dose : * Bone Marrow: Platelets ( PLT ) ≥ 90 × 109 /L , absolute neutrophil count ( ANC ) ≥ 1.5 × 109 /L , hemoglobin ≥ 9 g/dL ; * Coagulation: INR ≤ 1.5 , APTT ≤ 1.5 × ULN ; * Liver function: Liver function is basically normal, total bilirubin ≤ 1.5 × ULN ( total bilirubin in patients with Gilbert syndrome ≤ 3 × ULN can be enrolled), AST and ALT ≤ 2.5 × ULN (if there is liver metastasis, AST , ALT ≤ 5 × ULN ); * Renal function: serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (according to Cockcroft-Gault formula); * Cardiac function: left ventricular ejection fraction ( LVEF ) ≥ 50% ; female QT interval ( QTcF ) ≤ 470 ms , male ≤ 450 ms . 9. Be able to well communicate with the investigator and understand and comply with the requirements of this study.
Exclusion criteria
1. Cohort 1 : Previous use of eribulin and CCR8- targeting drugs; Cohort 2: previous use of CCR8-targeting drugs and nab-paclitaxel, unless the interval between the last dose of nab-paclitaxel in the adjuvant chemotherapy and first recurrence or metastasis is ≥12 months; 2. Have received radiotherapy, chemotherapy, traditional Chinese medicine with anti-tumor indications, and local therapy (interventional therapy but not including tumor biopsy, ablation therapy, etc.) within 2 weeks before trial drug treatment; 3. Adverse events from previous anti-tumor treatments have not recovered to ≤ grade 1 according to CTCAE v5.0 (except for ≤ grade 2 toxicities judged by the investigator to have no safety risk, such as alopecia, long-term toxicity caused by radiotherapy, etc.); 4. Patients with known brain metastases. Those with stable brain metastases can be enrolled; 5. Third space effusion that is clinically uncontrollable and unsuitable for enrollment; 6. Participants with≥ grade 3 allergies to antibody drugs previously; 7. Taking systemic corticosteroids (\>10 mg daily prednisone or equivalent dose) or other systemic immunosuppressive drugs (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate , thalidomide, and anti-tumor necrosis factor drugs), topical, ocular, intra-articular, intranasal, and inhaled corticosteroids are allowed; 8. Subjects with a known history of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, Guillain-Barre syndrome, multiplex syndrome sclerosis or glomerulonephritis, except autoimmune-related hypothyroidism treated with stable dose of hormone; 9. Known idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia, interstitial lung disease, severe radiation pneumonitis, or subjects with evidence of active pneumonia by chest CT scan screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 6 weeks | Objective Response Rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DoR | 6 weeks | Duration of overall response |
| DCR | 6 weeks | Disease control rate |
| PFS | 6 weeks | Progression-free survival |
| OS | 6 weeks | Overall survival |
| Adverse events | 6 weeks | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
Countries
China
Contacts
Primary ContactBiyun Wang
Outcome results
None listed