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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• ORR [Срок оценки: 6 weeks]

Вторичные конечные точки (5)

• DoR [Срок оценки: 6 weeks]
• DCR [Срок оценки: 6 weeks]
• PFS [Срок оценки: 6 weeks]
• OS [Срок оценки: 6 weeks]
• Adverse events [Срок оценки: 6 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT06387628 · LM108-IIT-202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗