Sac-TMT Plus KL-A167 in PD-L1+, HR+/HER2- Metastatic Breast Cancer After CDK4/6 Inhibitors

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.

Eligibility

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:

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   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);

Conditions2

Interventions1

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