Sac-TMT plus KL-A167 for PD-L1–positive, hormone receptor–positive/HER2–negative metastatic breast cancer after CDK4/6 inhibitors

A Phase II Study of Sacituzumab Tirumotecan (Sac-TMT) Combined With Tagitanlimab(KL-A167) in PD-L1-Positive, Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer Patients Previously Treated With CDK4/6 Inhibitors

This treatment combines Sac-TMT and KL-A167 to see if it can control disease in people with PD-L1–positive, HR+/HER2– metastatic breast cancer whose disease progressed after CDK4/6 inhibitors.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: Chemotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07258108 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-arm Phase II trial enrolling 35 patients with PD-L1–positive, HR+/HER2– metastatic breast cancer previously treated with CDK4/6 inhibitors. Patients receive intravenous Sac-TMT (5 mg/kg) plus KL-A167 (900 mg) every two weeks until disease progression or unacceptable toxicity. The primary endpoint is the 6-month progression-free survival rate by investigator assessment using RECIST v1.1, with secondary endpoints including PFS, ORR, DCR, DoR, OS, and safety. Tumor assessments are every 6 weeks for the first 6 months then every 12 weeks, and an exploratory analysis will correlate TROP2 and PD-L1 expression with outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18–75 with PD-L1–positive, HR+/HER2– metastatic breast cancer who progressed during or within 12 months after CDK4/6 inhibitor therapy (or on CDK4/6 for metastatic disease), have at least one measurable lesion, ECOG 0–1, and adequate organ function.

Not a fit: Patients with PD-L1–negative tumors, HER2‑positive disease, poor performance status, significant comorbid organ dysfunction, or prior intolerance to similar agents are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If effective, this combination could extend progression-free survival and offer a new treatment option for patients who progressed after CDK4/6 inhibitors.

How similar studies have performed: TROP2-directed therapies and PD‑1/PD‑L1 immunotherapies have shown activity in subsets of breast cancer, but this exact combination in PD-L1–positive, HR+/HER2– patients after CDK4/6 inhibitors is a novel approach with limited prior data.

Eligibility criteria

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);

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Fei Xu, MD — Sun Yat-sen University
• Study coordinator: Fei Xu, MD

Conditions: Breast Cancer