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

Official title

A Phase II Single Center Two Cohorts Trial of LM-108 in Combination With PD-1 Based Treatment for Patients With Recurrent or Metastatic Triple - Negative Breast Cancer

Overview

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

• Drug LM-108
  LM-108, 10mg/kg, d1, q6w
• Drug Toripalimab
  Toripalimab, 240 mg, d1, q3w
• Drug Eribulin
  Eribulin 1.4 mg/m2, d1, 8 , q3w
• Drug Nab paclitaxel
  Nab paclitaxel 125 mg/m2, d1, 8 , q3w

Primary outcome measures

• ORR [Time frame: 6 weeks]

Secondary outcome measures (5)

• DoR [Time frame: 6 weeks]
• DCR [Time frame: 6 weeks]
• PFS [Time frame: 6 weeks]
• OS [Time frame: 6 weeks]
• Adverse events [Time frame: 6 weeks]

Eligibility criteria

Inclusion criteria

• Age 18-75 years old (including boundary value), no gender limit;
• ECOG score 0-1;
• Expected survival ≥3 months;
• 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;
• 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.;
• Provide sufficient fresh tissue specimens for biomarker analysis before treatment;
• According to RECISTv1.1 standard, there is at least 1 measurable lesion;
• 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 .
• Be able to well communicate with the investigator and understand and comply with the requirements of this study.

Exclusion criteria

• 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;
• 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;
• 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.);
• Patients with known brain metastases. Those with stable brain metastases can be enrolled;
• Third space effusion that is clinically uncontrollable and unsuitable for enrollment;
• Participants with≥ grade 3 allergies to antibody drugs previously;
• 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;
• 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;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT06387628 · LM108-IIT-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗