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

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: YL201; Drug: Paclitaxel; Drug: Docetaxel; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Estimated): 440
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Medilink Study Team; Phone Number: 051262858368; Email: clinicaltrials@medilinkthera.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • 101
      • Contact: Study Coordinator

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Other malignancies within 5 years prior to first dose or currently concurrent malignancies.
2. 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).
3. Major surgery, significant traumatic injury within 4 weeks prior to first dose, or anticipated need for major surgery during study treatment
4. Any arterial thromboembolic event within 6 months prior to randomization, or venous thromboembolic events of Grade ≥ 3 according to NCI CTCAE version 5.0.
5. Known active tuberculosis (TB). Participants suspected of having active TB must undergo clinical evaluation to rule it out.
6. History of immunodeficiency or positive test for human immunodeficiency virus (HIV) antibodies. Participants with known active syphilis infection are also excluded.
7. Current active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
8. 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.
9. Women who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study period.
10. 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.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YL201; YL201 monotherapy	Drug: YL201; YL201, a B7H3 targeting ADC，administered on Day 1 of each cycle, intravenous infusion, every 3 weeks (Q3W).
Active Comparator: Control; Investigator's choice of Chemotherapy	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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization to the event of death from any cause.	Up to Approximately 36 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first occurrence of radiographic progression based on RECIST version 1.1 as determined by investigator or death from any cause, whichever occurs earlier.	Up to Approximately 36 Months
Overall response rate (ORR)	ORR is defined as the proportion of participants achieving a best overall response of confirmed Complete response (CR) or confirmed partial response (PR) as determined by investigator based on RECIST version 1.1.	Up to Approximately 36 Months
Disease control rate (DCR)	DCR is defined as the proportion of participants with complete response (CR), partial response (PR), or disease stabilization (SD) as determined by the investigator according to RECIST 1.1.	Up to Approximately 36 Months
Duration of Response (DOR)	DOR is defined as the time interval from the date of first documentation of objective response (CR or PR) to date of the first documentation of disease progression as determined by the investigator according to RECIST v1.1, or death due to any cause, whichever occurs first.	Up to Approximately 36 Months
Adverse Event (AE)	The incidence and severity of adverse events, with severity graded according to the NCI CTCAE v5.0 scale.	Up to Approximately 36 Months

Collaborators and Investigators

• Sponsor: MediLink Therapeutics (Suzhou) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): December 31, 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 30, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Camptothecin; Alkaloids; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; Irinotecan; Paclitaxel
• Other Study ID Numbers: YL201-CN-303-01

Drug and device information, study documents

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