LM-108 in Combination With PD-1 Based Treatment for Patients With Recurrent or Metastatic 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

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.

Study Overview

• Status: Recruiting
• Conditions: TNBC - Triple-Negative Breast Cancer
• Intervention / Treatment: Drug: LM-108; Drug: Toripalimab; Drug: Eribulin; Drug: Nab paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Biyun Wang; Phone Number: 18017312387; Email: pro_wangbiyun@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Biyun Wang; Phone Number: 18017312387; Email: pro_wangbiyun@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LM-108, toripalimab and eribulin	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
Experimental: LM-108, toripalimab and nab-paclitaxel	Drug: LM-108; LM-108, 10mg/kg, d1, q6w; Drug: Toripalimab; Toripalimab, 240 mg, d1, q3w; Drug: Nab paclitaxel; Nab paclitaxel 125 mg/m2, d1, 8 , q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	6 weeks
OS	Overall survival	6 weeks
DoR	Duration of overall response	6 weeks
DCR	Disease control rate	6 weeks
PFS	Progression-free survival	6 weeks

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; PD-1; TNBC; Triple-Negative Breast Cancer; CCR8
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: LM108-IIT-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No