A Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B003 Monotherapy, BL-B01D1+SI-B003 Combination Therapy and BL-B01D1+PD-1 Monoclonal Antibody in Patients With Locally Advanced or Metastatic Esophageal Cancer, Gastric Cancer, Colorectal Cancer and Other Gastrointestinal Tumors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 268
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
This phase II study is a clinical study to explore the efficacy and safety of SI-B003 Monotherapy, BL-B01D1+SI-B003 Combination Therapy and BL-B01D1+PD-1 Monoclonal Antibody in patients with locally advanced or metastatic esophageal cancer, gastric cancer, colorectal cancer and other gastrointestinal tumors.
详细描述
To explore the efficacy, safety and tolerability of SI-B003 Monotherapy, BL-B01D1+SI-B003 Combination Therapy and BL-B01D1+PD-1 Monoclonal Antibody in patients with locally advanced or metastatic esophageal cancer, gastric cancer, colorectal cancer and other gastrointestinal tumors, and to further explore the optimal dose and combination way.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sign the informed consent form voluntarily and follow the protocol requirements;
- •Gender is not limited;
- •Age: ≥18 years old and ≤75 years old;
- •Expected survival time ≥3 months;
- •Patients with locally advanced or metastatic esophageal cancer, gastric cancer, colorectal cancer and other gastrointestinal tumors;
- •Agreed to provide primary tumors or metastases 2 years archive of tumor tissue samples or fresh tissue samples;
- •At least one measurable lesion meeting the RECIST v1.1 definition was required;
- •ECOG 0 or 1;
- •The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
- •No blood transfusion, no use of cell growth factors and/or platelet-raising drugs within 14 days before screening, and organ function levels must meet the criteria;
- •Blood coagulation function: international standardization ratio of 1.5 or less, and the part activated clotting time live enzymes ULN 1.5 or less;
- •Urinary protein ≤2+ or ≤1000mg/24h;
- •For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, serum or urine must be negative for pregnancy, and must be non-lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.
排除标准
- •Antitumor therapy such as chemotherapy or biological therapy was used within 4 weeks or 5 half-lives before the first dose in this study; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil;
- •Cohort using BL-B01D1, previously treated with an ADC drug with topoisomerase I inhibitor as toxin; Immunomodulatory drugs were administered within 2 weeks before the first dose in this study;
- •Systemic corticosteroids were required within 2 weeks before the first dose of the study;
- •Had received immunotherapy and developed grade ≥3 irAE or grade ≥2 immune-related myocarditis according to the CSCO guidelines;
- •History of severe heart disease;
- •QT prolongation, complete left bundle branch block, III degree atrioventricular block;
- •Active autoimmune and inflammatory diseases;
- •Other malignant tumors were diagnosed within 5 years before the first dose in this study;
- •Presence of: a) poorly controlled diabetes mellitus before starting study treatment; b) poorly controlled hypertension; c) history of hypertensive crisis or hypertensive encephalopathy;
- •Pulmonary disease defined as grade ≥3 according to CTCAE v5.0; The patient was diagnosed with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition. Patients with existing or a history of interstitial lung disease;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
- •Patients with unstable pericardial effusion, pleural effusion, ascites and other serous cavity effusion;
- •Patients with active central nervous system metastasis;
- •Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any ingredient of BL-B01D1 or SI-B003;
- •Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
- •Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or hepatitis C virus infection;
- •Active infections requiring systemic therapy, such as severe pneumonia, bacteremia, sepsis, etc;
- •Enrolled in another clinical trial within 4 weeks before the first dose of this study;
- •Patients who received live vaccine within 4 weeks before the first dose;
- •Patients with a history of mental illness or drug abuse who are unable to cooperate with clinical trial requirements;
- •The investigator did not consider it appropriate to apply other criteria for participation in the trial.
研究组 & 干预措施
SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody
Participants received SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody in the first cycle (3 weeks). Participants who had a clinical benefit could receive additional cycles of additional treatment. Administration will be discontinued because of disease progression or intolerable toxicity or for other reasons.
干预措施: SI-B003 (Drug)
SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody
Participants received SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody in the first cycle (3 weeks). Participants who had a clinical benefit could receive additional cycles of additional treatment. Administration will be discontinued because of disease progression or intolerable toxicity or for other reasons.
干预措施: BL-B01D1 (Drug)
SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody
Participants received SI-B003, BL-B01D1+SI-B003 and BL-B01D1+PD-1 Monoclonal Antibody in the first cycle (3 weeks). Participants who had a clinical benefit could receive additional cycles of additional treatment. Administration will be discontinued because of disease progression or intolerable toxicity or for other reasons.
干预措施: PD-1 Monoclonal Antibody (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Up to approximately 24 months
ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
Recommended Phase II Dose (RP2D)
时间窗: Up to approximately 24 months
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study .
次要结局
- Duration of response (DOR)(Up to approximately 24 months)
- Progression-free survival (PFS)(Up to approximately 24 months)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Disease control rate (DCR)(Up to approximately 24 months)