lm-108 in combination with pd-1 based treatment for patients with recurrent or metastatic triple - negative breast cancer

Conditions: TNBC - Triple-Negative Breast Cancer

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.


Eligibility criteria:
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.

Keywords: immunotherapy pd-1 ccr8 triple-negative breast cancer tnbc