A Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma(PANKU-Esophagus01)

Prior treatment

• Chemotherapy, targeted therapy, biological therapy, etc., had been used within 4 weeks or 5 half-lives before randomization, and palliative radiotherapy and modern traditional Chinese medicine preparations approved by NMPA had been used within 2 weeks;
• Frontline received ADCs with topoisomerase I inhibitors as toxins;
• present with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition; A previous history of interstitial lung disease (ILD) or a suspicion of such disease on imaging during screening;
• Severe infections within 4 weeks before randomization; Evidence of pulmonary infection or active pulmonary inflammation within 2 weeks before randomization;
• serious unhealed wounds, ulcers, or fractures, or clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
• received other unmarketed investigational drugs or treatments within 4 weeks before randomization;
• subjects scheduled for vaccination or who received live vaccine within 28 days before study randomization;

Other illness

• History of severe heart disease and cerebrovascular disease;
• diagnosed with active malignancy within 3 years before randomization;
• Hypertension poorly controlled by two antihypertensive drugs;
• Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
• patients with inflammatory bowel disease, extensive bowel resection history, immune enteritis history, intestinal obstruction or chronic diarrhea;
• patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of BL-B01D1;
• had a history of autologous or allogeneic stem cell transplantation;
• Human immunodeficiency virus antibody positive, active hepatitis B virus infection or hepatitis C virus infection;
• a history of severe neurological or psychiatric illness;

Lab values

• Prolonged QT interval, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;

Other

• Patients with recurrent esophageal squamous cell carcinoma suitable for radical local treatment should be excluded;
• patients with poor glycemic control;
• patients with active central nervous system metastases;
• patients with massive or symptomatic effusions or poorly controlled effusions;
• Imaging examination showed that the tumor had invaded or wrapped around the large blood vessels in the abdomen, chest, neck, and pharynx;
• Other circumstances in which the investigator considered it inappropriate to participate in the trial because of complications or other circumstances.

• Voluntarily sign the informed consent and follow the requirements of the protocol;
• Age ≥18 years old;
• Expected survival time ≥3 months;
• Patients with recurrent or metastatic esophageal squamous cell carcinoma confirmed by histology or cytology;
• Consent to provide archival tumor tissue samples or fresh tissue samples of primary or metastatic lesions within 3 years;
• Must have at least one measurable lesion according to RECIST v1.1 definition;
• ECOG 0 or 1;
• Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
• No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
• No blood transfusion and no use of any cell growth factor drugs were allowed within 14 days before randomization, and the level of organ function had to be adequate;
• Urine protein ≤2+ or \< 1000mg/24h;
• A serum pregnancy test must be performed within 7 days before the start of treatment for premenopausal women who are likely to have children, and the result must be negative and must not be lactating; All enrolled patients should take adequate barrier contraception during the entire treatment cycle and for 6 months after the end of treatment.