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
Overview
- Phase
- Phase 2
- Intervention
- HLX43 DOSE 1
- Conditions
- Esophageal Cancer
- Sponsor
- Shanghai Henlius Biotech
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- ORR
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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;
- •The age of signing ICF is ≥ 18 years old and ≤ 75 years old;
- •Esophageal Squamous Cell Carcinoma (ESCC) confirmed by histopathology or cytology;
- •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.;
- •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;
- •Tumor tissue should be provided as much as possible for an evaluable PD-L1 expression result at Screening period；
- •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)；
- •The ECOG physical performance score of 0-1 in the week prior to randomization；
- •Expected survival ≥ 3 monthes；
- •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)；
Exclusion Criteria
- •History of any second malignant tumor within the first 2 years prior to randomization;
- •BMI \<17.5 kg/m2；
- •Symptomatic, untreated, or progressively worsening central nervous system (CNS) or leptomeninges metastases;
- •After appropriate intervention, uncontrollable pleural effusion, pericardial effusion or ascites still need to be drained frequently;
- •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;
- •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);
- •Subjects who are preparing for or have previously received an organ or bone marrow transplant;
- •Within the 2 weeks prior to randomization, there is the presence of an active systemic infectious disease requiring intravenous antibiotic treatment;
- •Used strong inhibitors or strong inducers of CYP2D6 or CYP3A within 2 weeks prior to randomization;
- •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;
Arms & Interventions
HLX43 DOSE 1
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)
Intervention: HLX43 DOSE 1
HLX43 DOSE 2
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)
Intervention: HLX43 DOSE 2
HLX43 DOSE 3
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)
Intervention: HLX43 DOSE 3
Outcomes
Primary Outcomes
ORR
Time Frame: up to 24 week
Objective response rate (ORR) (assessed by INV according to the RECIST v1.1 criteria)
PFS
Time Frame: 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
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.
Secondary Outcomes
- ORR(up to 24 weeks)
- PFS(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(From randomization to death from any cause (up to approximately 36 months))
- Incidence and severity of adverse events (AEs)(time from the date of the first dose of study drug until the date of death from any cause, assessed up to 24 months)