A Study of YL201 Versus Investigator's Choice of Chemotherapy in Participants With Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma After Failure of First-Line Therapy

Official title

A Randomized, Controlled, Multicenter Phase III Study of YL201 Versus Investigator's Choice of Chemotherapy in Participants With Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma After Failure of First-Line Therapy (TAISHAN-303)

Overview

This is a large clinical study carried out at multiple hospitals. Participants will be randomly assigned to one of two groups: one group will receive a new medicine called YL201, and the other group will receive standard chemotherapy chosen by the doctor. The purpose of the study is to see whether YL201 works better and is safer for people with locally advanced or metastatic esophageal squamous cell carcinoma whose first-line treatment has stopped working. The study will also look at how YL201 is processed in the body (Pharmacokinetics), whether it triggers any immune reactions, and whether certain biological markers can help predict how well it works.

Interventions

• Drug YL201
  YL201, a B7H3 targeting ADC，administered on Day 1 of each cycle, intravenous infusion, every 3 weeks (Q3W).
• Drug Paclitaxel
  175 mg/m², administered on Day 1 of each cycle, intravenous infusion, every 3 weeks (Q3W).
• Drug Docetaxel
  75 mg/m², administered on Day 1 of each cycle, intravenous infusion, every 3 weeks (Q3W).
• Drug Irinotecan
  125 mg/m², administered on Days 1 and 8 of each cycle, intravenous infusion, every 3 weeks (Q3W).

Primary outcome measures

• Overall Survival (OS) [Time frame: Up to Approximately 36 Months]

Secondary outcome measures (5)

• Progression-Free Survival (PFS) [Time frame: Up to Approximately 36 Months]
• Overall response rate (ORR) [Time frame: Up to Approximately 36 Months]
• Disease control rate (DCR) [Time frame: Up to Approximately 36 Months]
• Duration of Response (DOR) [Time frame: Up to Approximately 36 Months]
• Adverse Event (AE) [Time frame: Up to Approximately 36 Months]

Eligibility criteria

Inclusion criteria

• Age: ≥18 years;
• Voluntary participation in this study with signed informed consent and good compliance.
• ECOG PS score: 0-1;
• estimated life expectancy >3 months;
• Histologically or cytologically confirmed ESCC with unresectable locally advanced or metastatic disease
• Previously received one line of systemic standard therapy for unresectable locally advanced or metastatic ESCC and experienced disease progression
• Adequate organ function.
• At least one measurable lesion
• Willing to provide biopsy or archived tumor tissue.

Exclusion criteria

• Other malignancies within 5 years prior to first dose or currently concurrent malignancies.
• Prior treatment-related adverse events not resolved to ≤Grade 1 per CTCAE v5.0, except for alopecia (any grade), hyperpigmentation (any grade), peripheral neuropathy (≤ Grade 2), and lymphopenia (≤ Grade 3).
• Major surgery, significant traumatic injury within 4 weeks prior to first dose, or anticipated need for major surgery during study treatment
• Any arterial thromboembolic event within 6 months prior to randomization, or venous thromboembolic events of Grade ≥ 3 according to NCI CTCAE version 5.0.
• Known active tuberculosis (TB). Participants suspected of having active TB must undergo clinical evaluation to rule it out.
• History of immunodeficiency or positive test for human immunodeficiency virus (HIV) antibodies. Participants with known active syphilis infection are also excluded.
• Current active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Known allergy to any component of the investigational product; history of severe allergic reactions (e.g., anaphylactic shock); or known history of severe hypersensitivity reactions to other monoclonal antibodies or recombinant proteins, or previous severe infusion reactions.
• Women who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study period.
• Any disease, medical condition, organ dysfunction, or social/psychological circumstance that, in the investigator's judgment, may interfere with the participant's ability to sign the informed consent form (ICF), compromise cooperation or compliance with study procedures, or affect the interpretation of study results. This includes, but is not limited to, psychiatric disorders, substance/alcohol abuse, or a history of drug abuse.

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

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 81 centers

• 144 — Anqing
• 135 — Bengbu
• 133 — Hefei
• 143 — Hefei
• 129 — Beijing
• 161 — Beijing
• 183 — Beijing
• 119 — Chongqing
• … and 73 more centers

Identifiers

NCT: NCT07487896 · YL201-CN-303-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗