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

NCT07258108 | Recruiting Phase 2

• 1 other identifier: SYSU-2025
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 6-month progression-free survival rate (PFS)

  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.

  6 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  1 year

• Progression-Free Survival (PFS)

  1 year

• Disease Control Rate (DCR)

  1 year

• Duration of Response (DoR)

  1 year

• Overall survival (OS)

  1 year

Study Arms (1)

Sacituzumab Tirumotecan(Sac-TMT) plus Tagitanlimab(KL-A167)

EXPERIMENTAL

Sac-TMT (5 mg/kg, Q2W) in combination with KL-A167 (900 mg, Q2W) administered intraveno

Drug: Lucanisatuzumab plus tagolimumab

Interventions

Lucanisatuzumab plus tagolimumab DRUG

Each participant receives Lucanisatuzumab plus tagolimumab intravenously.

Sacituzumab Tirumotecan(Sac-TMT) plus Tagitanlimab(KL-A167)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old.
• HR+/HER2- breast cancer (BC), meeting the following conditions:
• HR+/HER2-; HER2-(IHC 0 or 1+); IHC 2+(FISH negative); HR+ (ER and/or PR IHC showed ≥1%);
• 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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• Complete blood count: Neutrophil count ≥ 1.5×10\^9/L; platelets ≥ 100×10\^9/L; hemoglobin ≥ 9 g/dL.
• 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.
• Renal function: Creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula).
• Coagulation function: INR, APTT, and PT ≤ 1.5× ULN.
• 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.

You may not qualify if:

• Received any of the following treatments during the advanced stage:
• Chemotherapy;
• any targeted therapy against topoisomerase I including antibody-drug conjugates (ADCs);
• immune checkpoint agonists (e.g., anti-PD-1/L1antibodies, anti-CTLA-4 antibodies), or any immune cell therapy;
• Recurrence or metastasis within 12 months of the last chemotherapy in the early stage;
• Subjects with central nervous system (CNS) metastases. For subjects with brain metastases who have previously received local therapy,
• 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);

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Fifth Affiliated Hospital, Sun Yat-Sen University: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Fei Xu, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fei Xu, MD

CONTACT

+86-13711277870; xufei@sysucc.org.cn

Kuikui Jiang, MD

CONTACT

+86-15210589011; jiangkk@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 2, 2025
• Study Start: November 13, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: May 8, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)