Phase II Study of HLX43 Monotherapy or Combined With Immune Checkpoint Inhibitors in Patients With Locally Advanced, Recurrent, or Metastatic Triple-negative Breast Cancer.

A Phase II Study to Evaluate the Efficacy and Safety of HLX43 (an Anti-PD-L1 ADC) as a Monotherapy or in Combination With Immune Checkpoint Inhibitors in Subjects With Locally Advanced, Recurrent or Metastatic Triple-negative Breast Cancer (TNBC).

The study is being conducted to explore the reasonable dosage and evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) as a monotherapy or in combination with immune checkpoint inhibitors in Subjects with locally advanced, recurrent or metastatic triple-negative breast cancer (TNBC).

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer (Triple Negative Breast Cancer (TNBC))
• Intervention / Treatment: Drug: HLX43 DOSE 1 IN ≥2L TNBC; Drug: HLX43 DOSE 2 IN ≥2L TNBC; Drug: HLX43 DOSE1 IN 1L TNBC; Drug: HLX43 DOSE 2 IN 1L TNBC; Drug: HLX43 DOSE 1 + HLX10; Drug: HLX43 DOSE2 + HLX10

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiangyun Wang; Phone Number: 86-13391626886; Email: Xixangyun_Wang@henlius.com

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Affiliated Cancer Hospital
      • Contact: Tong Liu, Dr; Phone Number: 86-15945953777; Email: Liutong@hrbmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntary written informed consent obtained before any study procedures.
2. Age ≥ 18 years at consent; no gender restriction.

3. Histopathologically confirmed TNBC: ER < 1%, PR < 1%, HER2 IHC 0/1+/2+ with no FISH amplification.

   • Phase I: Recurrent or metastatic TNBC after ≥1 prior line of standard systemic therapy.
   • Phase II: Unresectable locally advanced, recurrent, or metastatic TNBC with no prior systemic anti-cancer therapy for this stage (palliative radiotherapy to metastases allowed; neoadjuvant/adjuvant therapy permitted if completed ≥6 months before recurrence/metastasis).

4. At least one RECIST v1.1-measurable lesion documented within 4 weeks before randomization.

   Note: Target lesions must not be in irradiated fields or the CNS. If only measurable lesion is irradiated, imaging must confirm progression post-radiotherapy.

5. Archival FFPE tumor tissue (≤6 months old, ≤2 years max) for PD-L1 testing; fresh biopsy acceptable if archival tissue is unavailable or inadequate.

   Note: Specimens must be non-irradiated FFPE blocks/slides with pathology report confirming malignancy and adequacy.

6. Washout: ≥3 weeks (or 5 half-lives, whichever is shorter) after major surgery, radiotherapy (except palliative bone RT), chemotherapy, targeted therapy, or immunotherapy; ≥1 week after minor surgery or anti-tumor TCM. All treatment-related AEs resolved to CTCAE v6.0 Grade ≤1 (stable Grade 2 peripheral neuropathy and alopecia exempted).
7. ECOG PS 0-1, assessed ≤7 days before randomization.
8. Life expectancy >3 months.
9. Adequate hematologic, hepatic, and renal function per labs ≤7 days before randomization.

Exclusion Criteria:

1. Prior topoisomerase I-targeting therapy (e.g., irinotecan, topotecan, or ADCs).
2. Second primary malignancy within 2 years before randomization (except cured carcinoma in situ or stage I tumors).
3. Prior grade ≥3 immune-related adverse event during immunotherapy.
4. Uncontrolled, recurrent malignant pleural, pericardial, or ascitic effusions requiring repeated drainage.
5. Active CNS metastases, spinal cord compression, or carcinomatous meningitis.
6. Clinically significant pulmonary impairment.
7. Uncontrolled cardiovascular or cerebrovascular disease .
8. Active systemic infection requiring IV antibiotics within 2 weeks before randomization.
9. Moderate or strong CYP2D6/CYP3A inhibitor or inducer use within 2 weeks before randomization.
10. Systemic corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressants within 2 weeks before randomization .
11. Active or suspected autoimmune disease .
12. Live or attenuated live vaccine within 4 weeks before randomization.
13. Hypersensitivity to mAbs, large-molecule biologics, or drug formulation excipients.
14. Active pulmonary tuberculosis.
15. Known immunodeficiency.
16. Active HBV , HCV , or HBV/HCV co-infection.
17. Pregnancy or lactation.
18. Participation in another interventional trial within 30 days before consent .
19. Any condition posing unacceptable safety risk or interfering with study conduct per investigator judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: armA: HLX43 DOSE 1 in ≥2L TNBC; Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)	Drug: HLX43 DOSE 1 IN ≥2L TNBC; Dose 1; HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.
Experimental: armB: HLX43 DOSE 2 in ≥2L TNBC; Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)	Drug: HLX43 DOSE 2 IN ≥2L TNBC; Dose 2; HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.
Experimental: armC: HLX43 DOSE 1 in 1L TNBC; Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)	Drug: HLX43 DOSE1 IN 1L TNBC; HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.
Experimental: armD: HLX43 DOSE 2 in 1L TNBC; Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)	Drug: HLX43 DOSE 2 IN 1L TNBC; HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.
Experimental: armE: HLX43 DOSE 1+ HLX10 in 1L TNBC; Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)	Drug: HLX43 DOSE 1 + HLX10; HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8. HLX10 is a humanized anti-PD-1 monoclonal antibody that functions as an immune checkpoint inhibitor.
Experimental: armF: HLX43 DOSE 2+ HLX10 in 1L TNBC; Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)	Drug: HLX43 DOSE2 + HLX10; HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8. HLX10 is a humanized anti-PD-1 monoclonal antibody that functions as an immune checkpoint inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective response rate (ORR) (assessed by BICR according to the RECIST v1.1 criteria)	up to 24 weeks
PFS	Defined as the time (in months) from randomization to the first confirmed and documented progressive disease or death (whichever occurs first) as assessed by BICR according to the RECIST v1.1 criteria.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Estimated): April 25, 2026
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): May 22, 2028

Study Registration Dates

• First Submitted: March 17, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

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; Triple Negative Breast Neoplasms
• Other Study ID Numbers: HLX43-BC202

Drug and device information, study documents

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