A Phase II Clinical Study to Evaluate HLX43 in Patients With Recurrent/Metastatic ESCC Failed or Intolerance to Standard Therapy

A Phase II Clinical Study to Evaluate the Efficacy and Safety of HLX43 (Anti-PD-L1 ADC) in Patients With Recurrent/Metastatic Esophageal Squamous Cell Carcinoma (ESCC) Failed or Intolerance to Standard First-line Therapy

The study is being conducted to explore the reasonable dosage and evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in Patients with Recurrent/Metastatic Esophageal Squamous Cell Carcinomar (ESCC) Failed or Intolerance to Standard First-Line Therapy.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: HLX43

Detailed Description

This study is an open-label phase II clinical study to explore the reasonable dosage and evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in Patients with Recurrent/Metastatic Esophageal Squamous Cell Carcinomar (ESCC) Failed or Intolerance to Standard First-Line Therapy.

In this study, eligible subjects will be randomized at 1:1:1 ratio, and the patients will be administered with HLX43 at different doses via intravenous infusion.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jinming Yu, Dr.; Phone Number: 0531-67626971; Email: sdyujinming@126.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital
      • Contact: Jinming Yu, PhD; Phone Number: 13806406293; Email: sdyujinming@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Volunteer to participate in clinical research; To fully understand and understand this study and to sign the Informed Consent Form (ICF); Willing to follow and able to complete all test procedures;
2. The age of signing ICF is ≥ 18 years old and ≤ 75 years old;
3. Esophageal Squamous Cell Carcinoma (ESCC) confirmed by histopathology or cytology;
4. Patients with advanced esophageal squamous cell carcinoma who have failed or are intolerant to prior first-line standard therapy (for patients with PD-L1 expression positive [CPS ≥1], first-line standard therapy is defined as platinum-based chemotherapy and immune checkpoint inhibitor [ICI] therapy; for patients with PD-L1 expression negative [CPS <1], first-line standard therapy is defined as platinum-based chemotherapy). Intolerable toxicity refers to the occurrence of CTCAE grade ≥3 adverse events.;
5. Within 4 weeks prior to the first administration of the medication, at least one measurable target lesion must be evaluated according to the RECIST v1.1 criteria;
6. Tumor tissue should be provided as much as possible for an evaluable PD-L1 expression result at Screening period；
7. Before the initial administration of the study drug, there should be at least a 3-week interval or 5 times the half-life of the last cytotoxic chemotherapy, immunotherapy, or biological therapy, whichever is shorter. There should be at least a 2-week interval from the previous small molecule targeted therapy, at least a 1-week interval from traditional Chinese medicine treatment with antitumor indications or minor surgery. Additionally, treatment-related adverse events (AEs) should have recovered to NCI-CTCAE grade ≤ 1 (except for grade 2 peripheral neurotoxicity and alopecia)；
8. The ECOG physical performance score of 0-1 in the week prior to randomization；
9. Expected survival ≥ 3 monthes；
10. Laboratory tests within the previous week confirm adequate organ function (within 14 days prior to the first dose of medication, without receiving interventions such as blood transfusions, granulocyte colony-stimulating factor, or recombinant human thrombopoietin)；
11. Male and female subjects of childbearing potential must agree to use at least one highly effective method of contraception during the trial and for at least 6 months after the last dose of the study drug. Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.

Exclusion Criteria:

1. History of any second malignant tumor within the first 2 years prior to randomization;
2. BMI <17.5 kg/m2；
3. Symptomatic, untreated, or progressively worsening central nervous system (CNS) or leptomeninges metastases;
4. After appropriate intervention, uncontrollable pleural effusion, pericardial effusion or ascites still need to be drained frequently;
5. A history of ≥ grade 3 radiation pneumonia; A history of (non-infectious) interstitial lung disease (ILD) requiring steroid use, or a current ILD, or suspected ILD cannot be ruled out by imaging at the time of screening; Or there are lung diseases leading to clinical severe respiratory impairment;
6. Subjects exhibit poorly controlled cardiovascular clinical symptoms or diseases, including but not limited to: (1) NYHA class II or above heart failure, or left ventricular ejection fraction (LVEF) < 50%; (2) unstable angina; (3) myocardial infarction or cerebrovascular accident within the last 6 months (excluding lacunar infarction, minor ischemic stroke, or transient ischemic attack); (4) uncontrolled arrhythmias (including QTc interval ≥ 450 ms for males, ≥ 470 ms for females) (QTc interval calculated by Fridericia's formula); (5) poorly controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg despite active treatment);
7. Subjects who are preparing for or have previously received an organ or bone marrow transplant;
8. Within the 2 weeks prior to randomization, there is the presence of an active systemic infectious disease requiring intravenous antibiotic treatment;
9. Used strong inhibitors or strong inducers of CYP2D6 or CYP3A within 2 weeks prior to randomization;
10. Received systemic corticosteroids (prednisone >10 mg/day or an equivalent dose of similar drugs) or other immunosuppressive treatments within 14 days prior to the first dose; with the following exceptions: use of topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids; short-term use of corticosteroids for prophylactic treatment during situations such as the use of contrast agents;
11. History of adverse events leading to permanent discontinuation of immunotherapy; or a history of grade 2 or higher immune-related pneumonitis or myocarditis;
12. Active or suspected autoimmune disease. Patients with autoimmune-related hypothyroidism who are undergoing thyroid hormone replacement therapy are permitted to participate in the study; patients with controlled Type 1 diabetes mellitus receiving insulin therapy are also allowed to participate in the study;
13. Live vaccinations or attenuated live vaccinations should not be administered within 4 weeks prior to the initial dosing. Administration of inactivated viral vaccines for seasonal influenza is permitted;
14. Known history of severe allergic reactions to macromolecular protein preparations/monoclonal antibodies, or allergy to components of the trial drug formulation；previous treatment with antibody-drug conjugates (ADCs) using a topoisomerase I inhibitor as the payload;
15. Active tuberculosis;
16. Human immunodeficiency virus (HIV) infection;
17. Pregnant or lactating women;
18. The researcher deems that the subject has any other factors that make them unsuitable for participation in this trial.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX43 DOSE 1; HLX43 2.0mg/kg every 3 weeks (Q3W)	Drug: HLX43; 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: HLX43 DOSE 2; HLX43 2.5mg/kg every 3 weeks (Q3W)	Drug: HLX43; 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: HLX43 DOSE 3; HLX43 3.0mg/kg every 3 weeks (Q3W)	Drug: HLX43; 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: HLX43 DOSE 4; HLX43 3.0mg/kg loading dose every 3 weeks (Q3W)	Drug: HLX43; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 INV 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 14 months
ORR	Objective response rate (ORR) (assessed by INV according to the RECIST v1.1 criteria)	up to 24 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective response rate (ORR) (assessed by the IRRC 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 the IRRC 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 14 months
OS	Overall Survival	From randomization to death from any cause (up to approximately 36 months)
Incidence and severity of adverse events (AEs)	severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version [v] 5.0	time from the date of the first dose of study drug until the date of death from any cause, assessed up to 24 months

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech
• Investigators: Principal Investigator: Jinming Yu, Dr., Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2025
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): June 5, 2027

Study Registration Dates

• First Submitted: January 7, 2025
• First Submitted That Met QC Criteria: January 9, 2025
• First Posted (Actual): January 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: HLX43-ESCC201

Drug and device information, study documents

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