A Phase Ill Randomized Controlled Clinical Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice as Second Line Treatment in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma After Failure of PD-1/PD-L1 Monoclonal Antibody in Combination With Platinum-based Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 497
- 试验地点
- 1
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This study is a registered phase Ill, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 in patients with recurrent or metastatic esophageal squamous cell carcinoma after failure of PD-1/PD-L1 monoclonal antibody in combination with platinum-based chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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;
- •Patients with recurrent esophageal squamous cell carcinoma suitable for radical local treatment should be excluded;
- •Frontline received ADCs with topoisomerase I inhibitors as toxins;
- •History of severe heart disease and cerebrovascular disease;
- •Prolonged QT interval, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
- •diagnosed with active malignancy within 3 years before randomization;
- •Hypertension poorly controlled by two antihypertensive drugs;
- •patients with poor glycemic control;
- •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;
- •Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
- •patients with active central nervous system metastases;
- •Severe infections within 4 weeks before randomization; Evidence of pulmonary infection or active pulmonary inflammation within 2 weeks before randomization;
- •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;
- •serious unhealed wounds, ulcers, or fractures, or clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
- •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;
- •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 circumstances in which the investigator considered it inappropriate to participate in the trial because of complications or other circumstances.
研究组 & 干预措施
Control group
Participants receive Irinotecan or paclitaxel or docetaxel 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.
干预措施: docetaxel (Drug)
Experimental Group
Participants receive BL-B01D1 as intravenous infusion for 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.
干预措施: BL-B01D1 (Drug)
Control group
Participants receive Irinotecan or paclitaxel or docetaxel 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.
干预措施: Irinotecan (Drug)
Control group
Participants receive Irinotecan or paclitaxel or docetaxel 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.
干预措施: paclitaxel (Drug)
结局指标
主要结局
Overall survival (OS)
时间窗: Up to approximately 24 months
Overall survival (OS) is defined as the time between the subject's randomization date and subject's death.
Progression-free survival (PFS)
时间窗: Up to approximately 24 months
Progression-free survival (PFS) as assessed by BIRC is defined as the time between the date subjects are randomized and the first observation of disease progression (based on BICR's image-based assessment) or death.
次要结局
- Objective Response Rate (ORR)(Up to approximately 24 months)
- Treatment Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Anti-drug antibody (ADA)(Up to approximately 24 months)
- Disease Control Rate (DCR)(Up to approximately 24 months)
- Duration of Response (DOR)(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)