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

Launched by FUDAN UNIVERSITY · Apr 23, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment combining LM-108 with toripalimab and either nab-paclitaxel or eribulin for patients with recurrent or metastatic triple-negative breast cancer (TNBC). TNBC is a type of breast cancer that does not respond to certain hormones and proteins, making it more challenging to treat. The goal of the trial is to see how effective and safe this combination of medications is for patients who have advanced stages of this cancer.

To be eligible for the trial, participants need to be between 18 and 75 years old, have a specific score that indicates their overall health (an ECOG score of 0-1), and have an expected survival of at least three months. They must also have advanced TNBC that cannot be surgically removed or has spread to other parts of the body. Patients can be newly diagnosed or have had previous treatments, but they must meet certain criteria regarding their past therapies. Those who join the trial will receive the study drugs and will be monitored for their safety and how well the treatment works. It's important for interested patients to talk with their healthcare provider to see if they meet the eligibility requirements and to understand what participating in the trial would involve.

Gender

ALL

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.