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(PANKU-Esophagus02)

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.

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.