Sac-TMT Plus KL-A167 in PD-L1+, HR+/HER2- 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 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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Lucanisatuzumab plus tagolimumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fei Xu, MD; Phone Number: +86-13711277870; Email: xufei@sysucc.org.cn
• Study Contact Backup: Name: Kuikui Jiang, MD; Phone Number: +86-15210589011; Email: jiangkk@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun yat-sen University Cancer Center
      • Contact: Fei Xu, MD; Phone Number: +86-13711277870; Email: xufei@sysucc.org.cn
      • Contact: Kuikui Jiang, MD; Phone Number: +86-15210589011; Email: jiangkk@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

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);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacituzumab Tirumotecan(Sac-TMT) plus Tagitanlimab(KL-A167); Sac-TMT (5 mg/kg, Q2W) in combination with KL-A167 (900 mg, Q2W) administered intraveno	Drug: Lucanisatuzumab plus tagolimumab; Each participant receives Lucanisatuzumab plus tagolimumab intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The proportion of subjects achieving complete response (CR) or partial response (PR) relative to the total number of subjects	1 year
Progression-Free Survival (PFS)	The time from the first administration of study treatment to the first occurrence of radiographic disease progression or death, whichever occurs first	1 year
Disease Control Rate (DCR)	The proportion of subjects achieving complete response (CR), partial response (PR), or stable disease (SD) relative to the total number of subjects	1 year
Duration of Response (DoR)	The time interval from the first documented disease response to disease progression or death (whichever occurs first)	1 year
Overall survival (OS)	The time from the first administration of the study treatment to the participant's death from any cause	1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Fifth Affiliated Hospital, Sun Yat-Sen University
• Investigators: Principal Investigator: Fei Xu, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: November 20, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): December 2, 2025

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: SYSU-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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