Clinical Trial Evaluating TQB6411 Injection in Participant s With Esophageal Cancer

Official title

A Phase Ib/II Clinical Trial Evaluating the Safety and Efficacy of TQB6411 Injection in Participant s With Recurrent or Metastatic Esophageal Cancer Who Have Failed Prior PD-1/PD-L1 Inhibitor Plus Platinum-Based Chemotherapy

Overview

The Phase Ib stage of this study primarily aims to evaluate the tolerance and safety of TQB6411 Injection in participants with recurrent or metastatic Esophageal cancer who have previously failed treatment with PD-1/PD-L1 monoclonal antibodies combined with platinum-based chemotherapy. The Phase II stage primarily aims to evaluate the efficacy of TQB6411 Injection in this same participants population.

Interventions

• Drug TQB6411 Injection
  TQB6411 Injection is an antibody-drug conjugate (ADC) targeting Epidermal Growth Factor Receptor (EGFR)/c-Met.

Primary outcome measures

• Recommended Phase 2 Dose (RP2D) [Time frame: 3 mouths]
• Incidence and severity of adverse events [Time frame: 24 mouths]
• Progression-Free Survival (PFS) [Time frame: 24 mouths]

Secondary outcome measures (9)

• Objective Response Rate (ORR) [Time frame: 24 mouths]
• Disease Control Rate(Disease Control Rate=achieving Complete Response [CR] or+Partial Response [PR]+Stable Disease (SD) [Time frame: 24 mouths]
• Duration of Response (DOR) [Time frame: 24 mouths]
• Overall Survival (OS) [Time frame: 24 mouths]
• Peak plasma concentration (Cmax) [Time frame: Within 14 days after administration]
• Area Under the Concentration-time Curve (AUC0-t) [Time frame: Within 14 days after administration]
• Area Under the Concentration-time Curve (AUC0-∞) [Time frame: Within 14 days after administration]
• Peak time (Tmax) [Time frame: Within 14 days after administration]
• Number of subjects with incidence of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) [Time frame: 24 months]

Eligibility criteria

Inclusion criteria

• Participants voluntarily participate in this study, sign the informed consent form, and demonstrate good compliance.
• Age between 18 and 75 years old (inclusive)
• Eastern Cooperative Oncology Group (ECOG) score of 0-1
• Expected survival >12 weeks
• At least one measurable lesion per RECIST v1.1
• Laboratory criteria(no hematopoietic growth factor correction within 7 days)：

• Hemoglobin (HGB) ≥90 g/L;
• Absolute neutrophil count (NEUT) ≥1.5×10⁹/L;
• Platelets (PLT) ≥90×10⁹/L;
• Total bilirubin (TBIL) ≤1.5×ULN;
• Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×ULN (≤5×ULN if liver metastases present);
• Serum creatinine (CR) ≤1.3×ULNorcreatinine clearance rate (CCR) ≥50 mL/min;
• Histologically/cytologically confirmed recurrent or metastatic Esophageal cancer
• Failure/intolerance to prior PD-1/PD-L1 inhibitor plus platinum-based chemotherapy for recurrent/metastatic Esophageal Carcinoma (EC)
• Willingness to provide archived or fresh tumor tissue for biomarker analysis.
• Females of childbearing potential: Negative serum/urine pregnancy test within 7 days before enrollment and agreement to use effective contraception during and for 6 months post-study. Males: Agreement to use effective contraception during and for 6 months post-study.

Exclusion criteria

• Current or History of Other Malignancies
• Participants with any condition that may compromise venous access for drug administration or blood sampling are excluded.
• Participants with prior treatment-related adverse reactions that have not recovered to ≤ Grade 1 per CTCAE v5.0 criteria.
• Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose, Scheduled major surgery during the study intervention period, Non-healing wound, ulcer, or bone fracture at screening
• Participants with any bleeding/hemorrhagic event ≥ Grade 3 (per CTCAE v5.0) occurring within 4 weeks before the first dose are excluded
• History of Thromboembolic Events within 6 Months
• Poorly Controlled Active Viral Hepatitis
• Participants with active syphilis infection requiring antimicrobial therapy are excluded
• Participants with any of the following pulmonary conditions are excluded: active tuberculosis, idiopathic pulmonary fibrosis (IPF), organizing pneumonia, drug-induced/radiation pneumonitis requiring treatment, symptomatic active pneumonia, or history of interstitial lung disease (ILD) requiring therapy
• History of Substance Abuse or Psychiatric Disorders
• History of Allogeneic Transplantation (Bone Marrow or Solid Organ)
• History of Hepatic Encephalopathy
• Major Cardiovascular Diseases
• Active or Uncontrolled Severe Infections
• Renal Failure Requiring Dialysis (Hemodialysis/Peritoneal Dialysis)
• History of Immunodeficiency
• Poorly Controlled Autoimmune Disease
• Poorly Controlled Autoimmune Disease \& Epilepsy Requiring Treatment
• Poorly Controlled Diabetes
• Tumor-Related Symptoms and Treatment Considerations：

• Exclusion Criterion - Recent Anticancer Treatment (≤3 Weeks or Within 5 Half-Lives)
• Recent Use of National Medical Products Administration (NMPA) -Approved Anticancer Traditional Chinese Medicine (≤1 Week Prior to Treatment)
• Radiologically Confirmed Tumor Encasement of Major Vessels with High Bleeding Risk
• Uncontrolled Effusions Requiring Repeated Drainage
• Known to have spinal cord compression, leptomeningeal metastasis/carcinomatous meningitis, or symptomatic brain metastases with less than 4 weeks of symptom/imaging control.
• Known Hypersensitivity to Investigational Drug or Excipients
• Prior Treatment with Topoisomerase I Inhibitor-Based ADCs and/or Irinotecan Chemotherapy
• Prior Participation in Anticancer Clinical Trials Within 4 Weeks
• Investigator-Assessed Safety or Compliance Concerns

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 30 centers

• The Second Affiliated Hospital of Anhui Medical University — Hefei
• Cancer Hospital Chinese Academy of Medical Sciences — Beijing
• Fujian Cancer Hospital — Fuzhou
• Gansu Provincial Tumor Hospital — Lanzhou
• The First Affiliated Hospital of Shantou University Medical College — Shantou
• Guangxi Medical University Cancer Hospital — Nanning
• Guizhou Provincial People's Hospital — Guangxi
• The Second Affiliated Hospital of Zunyi Medical University — Zunyi
• … and 22 more centers

Identifiers

NCT: NCT07367516 · TQB6411-Ib/II-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗