A Study of BL-B01D1 in Combination With Tislelizumab ±5-Fluorouracil Versus Platinum-Based Chemotherapy Plus Tislelizumab as First-line Treatment in Patients With Unresectable, Locally Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma(PANKU-Esophagus02)

A Phase II/III Randomized Controlled Clinical Study of BL-B01D1 for Injection in Combination With Tislelizumab With or Without 5-Fluorouracil Versus Platinum-Based Chemotherapy Plus Tislelizumab as First-line Treatment in Patients With Unresectable, Locally Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

This trial is a registrational Phase II/III, randomized, controlled, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 in combination with tislelizumab ± 5-FU in patients with unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: BL-B01D1; Drug: Cisplatin; Drug: Tislelizumab; Drug: 5-Fluorouracil; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: 15013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Beijing Cancer Hospital
      • Contact: Lin Shen

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntarily sign the informed consent form and agree to follow the protocol requirements;
2. No gender restriction;
3. Age ≥18 years and ≤75 years at the time of signing the informed consent form;
4. Expected survival time ≥3 months;
5. Patients with unresectable, locally advanced recurrent or metastatic first-line esophageal squamous cell carcinoma;
6. Must have at least one measurable target lesion as defined by RECIST v1.1;
7. Must provide archived tumor tissue specimens from the primary or metastatic lesion within the past 3 years;
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
9. Toxicity from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
10. No severe cardiac dysfunction; left ventricular ejection fraction ≥50%;
11. Organ function levels must meet the specified requirements;
12. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN);
13. Urine protein ≤1+ or <1000 mg/24h;
14. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment; serum pregnancy test must be negative, and the patient must not be breastfeeding; all enrolled patients (regardless of male or female) must use adequate barrier contraception throughout the entire treatment period and for 7 months after the end of treatment.

Exclusion Criteria:

1. Patients with esophageal squamous cell carcinoma whose pathology indicates the presence of non-squamous carcinoma components;
2. Use of immunomodulatory drugs within 2 weeks prior to the first study drug administration;
3. Prior use of an ADC drug whose small-molecule toxin is a topoisomerase I inhibitor;
4. Patients with esophageal squamous cell carcinoma who are suitable for curative-intent local therapy;
5. Receipt of curative-intent radiotherapy, major surgery, etc., within 4 weeks prior to study randomization;
6. Ongoing long-term systemic corticosteroid therapy (e.g., >10 mg/day prednisone) prior to the first dose;
7. Prior immunotherapy targeting PD-1, PD-L1, or PD-L2;
8. History of severe heart disease or cerebrovascular disease;
9. Prolonged QTc interval, complete left bundle branch block, etc.;
10. Active autoimmune diseases and inflammatory diseases;
11. Diagnosis of active malignant tumor within 3 years prior to study randomization;
12. Hypertension poorly controlled by two antihypertensive agents;
13. Patients with poorly controlled blood glucose;
14. History of interstitial lung disease (ILD)/interstitial pneumonitis requiring steroid therapy, etc.;
15. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to screening;
16. Presence of large serous cavity effusions or serous cavity effusions, etc.;
17. Concomitant pulmonary diseases resulting in clinically severe respiratory function impairment;
18. Imaging findings indicating tumor invasion or encasement of major blood vessels in the abdomen, thorax, neck, or pharynx;
19. Tumor invasion or compression of the trachea or bronchi causing any clinical symptoms such as cough;
20. Patients with esophageal fistula caused by tumor invasion of adjacent organs, or patients assessed by the investigator as being at risk of developing esophageal fistula;
21. Patients with tracheal or esophageal stent placement due to any cause;
22. Participants with clinically significant bleeding or an obvious bleeding tendency within 4 weeks prior to signing the informed consent form;
23. BMI < 18.5 kg/m² at screening, or weight loss ≥10% within 2 months prior to screening;
24. Patients with active central nervous system metastases;
25. Patients with a history of allergy to recombinant humanized antibodies or chimeric human-mouse antibodies, or allergy to any excipient component of BL-B01D1;
26. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
27. Positive for human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
28. Severe infection within 4 weeks prior to study randomization, etc.;
29. History of severe neurological or psychiatric disorders;
30. Patients with a history of substance abuse that precludes compliance with clinical trial requirements;
31. Severe, non-healing wound, ulcer, or bone fracture within 4 weeks prior to signing informed consent;
32. Patients with inflammatory bowel disease, history of extensive bowel resection, history of immune-mediated enteritis, intestinal obstruction, or chronic diarrhea, etc.;
33. Receipt of other unapproved clinical study drugs or treatments within 4 weeks prior to study randomization;
34. Trial participants planning to receive or having received live vaccine within 28 days prior to the first dose;
35. Pregnant or breastfeeding women;
36. Presence of other serious physical conditions, laboratory abnormalities, or poor compliance that may increase the risk of study participation, interfere with study results, or make the patient unsuitable for study participation in the investigator's opinion.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BL-B01D1 + tislelizumab + 5-FU; Participants receive BL-B01D1 + tislelizumab + 5-FU in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.	Drug: BL-B01D1; Administration by intravenous infusion for a cycle of 3 weeks.; Other Names: BMS-986507; iza-bren; izalontamab brengitecan; Drug: Tislelizumab; Administration by intravenous infusion for a cycle of 3 weeks.; Drug: 5-Fluorouracil; Administration by intravenous infusion for a cycle of 3 weeks.
Experimental: BL-B01D1 + tislelizumab; Participants receive BL-B01D1 + tislelizumab in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.	Drug: BL-B01D1; Administration by intravenous infusion for a cycle of 3 weeks.; Other Names: BMS-986507; iza-bren; izalontamab brengitecan; Drug: Tislelizumab; Administration by intravenous infusion for a cycle of 3 weeks.
Active Comparator: cisplatin + paclitaxel/5-FU+ tislelizumab; Participants receive cisplatin + paclitaxel/5-FU+ tislelizumab in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.	Drug: Cisplatin; Administration by intravenous infusion for a cycle of 3 weeks.; Drug: Tislelizumab; Administration by intravenous infusion for a cycle of 3 weeks.; Drug: 5-Fluorouracil; Administration by intravenous infusion for a cycle of 3 weeks.; Drug: Paclitaxel; Administration by intravenous infusion for a cycle of 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival (OS) is defined as the time between the day the subject is randomized and the subject's death.	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS).	Up to approximately 24 months
Disease Control Rate (DCR)	Disease Control Rate (DCR) : Percentage of all randomized subjects who rated the best overall response (BOR) as complete response (CR), partial response (PR), and disease stabilization (SD) according to RECIST 1.1 criteria.	Up to approximately 24 months
Duration of Response (DOR)	Duration of Response (DOR) : defined as the period from the date when tumor response is first recorded to the date when objective tumor progression is first recorded or the date of death.	Up to approximately 24 months
Treatment Emergent Adverse Event (TEAE)	TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-B01D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B01D1.	Up to approximately 24 months
Anti-drug antibody (ADA)	Frequency of anti-BL-B01D1 antibody (ADA) will be investigated.	Up to approximately 24 months
Progression-free survival (PFS)	Progression-free survival (PFS) as assessed by BICR is defined as the time between the date subjects were randomized and the first observation of disease progression (based on BICR's image-based assessment) or death.	Up to approximately 24 months
Time to Response (TTR)	Time to Response (TTR) : For trial participants with objective response (BOR of CR or PR), the time from randomization to the first documented response (CR or PR, whichever occurs first).	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 28, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Taxoids; Cyclodecanes; Diterpenes; Pyrimidines; Uracil; Pyrimidinones; Platinum Compounds; Fluorouracil; Paclitaxel; Cisplatin; tislelizumab
• Other Study ID Numbers: BL-B01D1-315

Drug and device information, study documents

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