Combination of LM-108 and PD-1 treatment for advanced triple-negative breast cancer

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

This study is testing a new combination of treatments for people with advanced triple-negative breast cancer to see if it helps them feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, methotrexate, cyclophosphamide, prednisone, toripalimab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06387628 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of LM-108 in combination with toripalimab and either nab-paclitaxel or eribulin for patients with recurrent or metastatic triple-negative breast cancer (TNBC). The study aims to determine how well this combination works as a first-line or subsequent treatment option. Participants will be monitored for their response to the treatment and any potential side effects. The trial includes patients with advanced TNBC who have specific eligibility criteria regarding their cancer status and previous treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with unresectable or metastatic triple-negative breast cancer who have had prior treatment and meet specific health criteria.

Not a fit: Patients with early-stage or operable triple-negative breast cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced triple-negative breast cancer.

How similar studies have performed: Other studies have shown promise with immunotherapy approaches in treating triple-negative breast cancer, but this specific combination is being evaluated for the first time.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Biyun Wang

Conditions TNBC - Triple-Negative Breast Cancer; Immunotherapy; PD-1; CCR8; Triple-Negative Breast Cancer; TNBC