Breast Cancer
Conditions
Brief summary
This is a Phase II single-arm study designed to evaluate the efficacy and safety of Sac-TMT + KL-A167 in 35 patients with PD-L1+, HR+/HER2- metastatic breast cancer who previously treated with CDK4/6 inhibitor. The primary endpoint is the 6-month PFS rate. Treatment will continue until disease progression or intolerable toxicity, with periodic imaging assessments and survival follow-up.
Detailed description
This study is a prospective, single-arm, multicenter Phase II study designed to evaluate the efficacy and safety of Sac-TMT in combination with KL-A167 for the treatment of PD-L1-positive, HR+/HER2- metastatic breast cancer patients who previously treated with CDK4/6. The study plans to enroll 35 patients. The primary endpoint is the 6-month progression-free survival (PFS) rate assessed by the investigator (RECIST v1.1). Secondary endpoints include PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS), and safety. An exploratory endpoint is to analyze the correlation between TROP2 and PD-L1 expression and efficacy. The treatment regimen consists of intravenous administration of Sac-TMT (5 mg/kg, Q2W) combined with KL-A167 (900 mg, Q2W). Treatment will continue until disease progression or occurrence of intolerable toxicity. Tumor assessments will be conducted every 6 weeks for the first 6 months, followed by every 12 weeks thereafter. Safety follow-up will occur after treatment completion, with telephone follow-ups every 3 months to collect survival and subsequent treatment information.
Interventions
DRUGLucanisatuzumab plus tagolimumab
Each participant receives Lucanisatuzumab plus tagolimumab intravenously.
Sponsors
Sun Yat-sen University
Fifth Affiliated Hospital, Sun Yat-Sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 18-75 years old. 2. HR+/HER2- breast cancer (BC), meeting the following conditions: 1. HR+/HER2-; HER2-(IHC 0 or 1+); IHC 2+(FISH negative); HR+ (ER and/or PR IHC showed ≥1%); 2. Tumor stage: Locally advanced, recurrent, or metastatic HR+/HER2- breast cancer; 3) Disease progression during or within 12 months after completion of adjuvant endocrine therapy based on a CDK4/6 inhibitor, or disease progression on CDK4/6 inhibitor treatment for metastatic disease; 4) PD-L1 positive (CPS ≥ 1); 5) At least one measurable target lesion as assessed by the investigator per RECIST 1.1; 6) Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy more than 12 weeks; 7) Adequate organ function, defined as: <!-- --> 1. Complete blood count: Neutrophil count ≥ 1.5×10\^9/L; platelets ≥ 100×10\^9/L; hemoglobin ≥ 9 g/dL. 2. Liver function: AST, ALT, and ALP ≤ 2.5× ULN; total bilirubin ≤ 1.5× ULN; ALT and AST ≤ 5× ULN, TBIL ≤ 2× ULN for patients with liver metastases; ALP ≤ 5× ULN for patients with liver or bone metastases. 3. Renal function: Creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula). 4. Coagulation function: INR, APTT, and PT ≤ 1.5× ULN. 5. Cardiac function: ECHO or MUGA scan indicating LVEF ≥ 50%. 8) For female participants of childbearing potential and male participants with reproductive potential, effective medical contraceptive measures must be implemented from the time of signing the informed consent until six months after the last administration; 9) Voluntary participation in the study with signed informed consent, demonstrated good compliance, and willingness to follow up as required.
Exclusion criteria
1. Received any of the following treatments during the advanced stage: 1. .Chemotherapy; 2. .any targeted therapy against topoisomerase I including antibody-drug conjugates (ADCs); 3. . immune checkpoint agonists (e.g., anti-PD-1/L1antibodies, anti-CTLA-4 antibodies), or any immune cell therapy; 2. Recurrence or metastasis within 12 months of the last chemotherapy in the early stage; 3. Subjects with central nervous system (CNS) metastases. For subjects with brain metastases who have previously received local therapy, 4. Other malignancies within 5 years prior to dosing (excluding locally treated and cured tumors such as basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-month progression-free survival rate (PFS) | 6 months | The proportion of subjects who remained free of radiographic disease progression or death within 6 months of receiving the first dose of study treatment, relative to the total number of subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 1 year | The proportion of subjects achieving complete response (CR) or partial response (PR) relative to the total number of subjects |
| Progression-Free Survival (PFS) | 1 year | The time from the first administration of study treatment to the first occurrence of radiographic disease progression or death, whichever occurs first |
| Disease Control Rate (DCR) | 1 year | The proportion of subjects achieving complete response (CR), partial response (PR), or stable disease (SD) relative to the total number of subjects |
| Duration of Response (DoR) | 1 year | The time interval from the first documented disease response to disease progression or death (whichever occurs first) |
| Overall survival (OS) | 1 year | The time from the first administration of the study treatment to the participant's death from any cause |
Countries
China
Contacts
CONTACTFei Xu, MD
CONTACTKuikui Jiang, MD
PRINCIPAL_INVESTIGATORFei Xu, MD
Sun Yat-sen University
Outcome results
None listed