LM-108 in Combination With PD-1 Based Treatment for Patients With Recurrent or Metastatic Triple - Negative Breast Cancer

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 confirmedadvanced 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 tumorswithout 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 byimmunohistochemistry 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 diseaseprogression or intolerable toxicity. In this situation, patients are allowed to beenrolled: the time between the last intravenous dose of adjuvant chemotherapy andfirst recurrence or metastasis is ≤6 months. Cohort 2: no prior line at recurrenceor metastasis setting is allowed, the time between the last intravenous dose ofadjuvant 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 ≥ 50mL/min (according to Cockcroft-Gault formula);

• Cardiac function: left ventricular ejection fraction ( LVEF ) ≥ 50% ; female QTinterval ( QTcF ) ≤ 470 ms , male ≤ 450 ms .

9. Be able to well communicate with the investigator and understand and comply with therequirements of this study.

Exclusion Criteria:

1. Cohort 1 : Previous use of eribulin and CCR8- targeting drugs; Cohort 2: previoususe of CCR8-targeting drugs and nab-paclitaxel, unless the interval between the lastdose of nab-paclitaxel in the adjuvant chemotherapy and first recurrence ormetastasis is ≥12 months;

2. Have received radiotherapy, chemotherapy, traditional Chinese medicine withanti-tumor indications, and local therapy (interventional therapy but not includingtumor biopsy, ablation therapy, etc.) within 2 weeks before trial drug treatment;

3. Adverse events from previous anti-tumor treatments have not recovered to ≤ grade 1according to CTCAE v5.0 (except for ≤ grade 2 toxicities judged by the investigatorto 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 beenrolled;

5. Third space effusion that is clinically uncontrollable and unsuitable forenrollment;

6. Participants with≥ grade 3 allergies to antibody drugs previously;

7. Taking systemic corticosteroids (>10 mg daily prednisone or equivalent dose) orother systemic immunosuppressive drugs (including but not limited to prednisone,dexamethasone, cyclophosphamide, azathioprine, methotrexate , thalidomide, andanti-tumor necrosis factor drugs), topical, ocular, intra-articular, intranasal, andinhaled corticosteroids are allowed;

8. Subjects with a known history of autoimmune diseases, including but not limited tomyasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus,rheumatoid arthritis, Guillain-Barre syndrome, multiplex syndrome sclerosis orglomerulonephritis, except autoimmune-related hypothyroidism treated with stabledose of hormone;

9. Known idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitisobliterans), drug-induced pneumonia, idiopathic pneumonia, interstitial lungdisease, severe radiation pneumonitis, or subjects with evidence of active pneumoniaby chest CT scan screening.