A Phase II Clinical Study to Evaluate the Efficacy and Safety of BL-B01D1 Monotherapy, SI-B003 Monotherapy and BL-B01D1+SI-B003 Combination Therapy (BL-B01D1+SI-B003) in Patients With Recurrent or Metastatic Cervical Cancer and Other Gynecological Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
Objective: To explore the efficacy, safety and tolerability of BL-B01D1, SI-B003 and BL-B01D1+SI-B003 in patients with recurrent or metastatic cervical cancer and other gynecological malignancies, and to further explore the optimal dose and mode of combination.
详细描述
Objective
To explore the efficacy of BL-B01D1 monotherapy, SI-B003 monotherapy, and BL-B01D1+SI-B003 combination therapy in patients with recurrent or metastatic cervical cancer. To explore the safety and tolerability of BL-B01D1 monotherapy, SI-B003 monotherapy and BL-B01D1+SI-B003 combination therapy in patients with recurrent or metastatic cervical cancer and other gynecological malignancies, and to further explore the optimal dose and mode of combination therapy.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Subject volunteered to participate in the study and signed an informed consent;
- •Women aged ≥18 years and ≤75 years;
- •Expected survival time ≥3 months;
- •ECOG score 0-1;
- •Gynecological malignancies such as recurrent or metastatic cervical cancer confirmed by histopathology and/or cytology after failure or intolerance to standard treatment or for which no standard treatment is available;
- •Agree to provide 10 surgical specimens or fresh tissue samples of primary or metastatic tumors within 3 years;
- •At least one measurable lesion meeting the RECIST v1.1 definition was required;
- •No blood transfusion, colony-stimulating factor, any cell growth factor injection, or albumin injection were allowed within 14 days before the first use of the study drug, and the organ function level must meet the requirements;
- •Urine protein ≤2+ or ≤1000g/24h;
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
- •The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
- •For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, a serum or urine pregnancy test must be negative, and the patient 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
- •Prior treatment with an ADC drug with a topoisomerase I inhibitor as a toxin;
- •Use of antineoplastic therapy within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral fluorouracil or palliative radiotherapy within 2 weeks before the first dose;
- •Cohort_B and Cohort_C with a history of immunotherapy and grade ≥3 irAE or grade ≥2 immune-related myocarditis;
- •Cohort_B, Cohort_C, who had received an immunomodulatory drug within 14 days before the first dose of study drug;
- •Had a history of serious cardiovascular and cerebrovascular diseases;
- •Active autoimmune and inflammatory diseases;
- •Other malignant tumors that progressed or required treatment within 5 years before the first dose;
- •A history of ILD requiring steroid therapy, current ILD, or suspected ILD at screening that could not be ruled out by imaging;
- •History of poorly controlled diabetes mellitus, poorly controlled hypertension, or hypertensive crisis or hypertensive encephalopathy before the first medication;
- •New onset of deep vein thrombosis within 14 days before screening or pulmonary embolism within 6 months;
- •Patients with active central nervous system metastases;
- •Patients with massive, symptomatic, poorly controlled, or unstable effusions;
- •Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of BL-B01D1's excipients;
- •Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
- •Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
- •Active infections requiring systemic therapy, such as severe pneumonia, bacteremia, sepsis, etc;
- •Had participated in another clinical trial within 4 weeks before the first dose;
- •Who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
- •Patients with a history of intestinal obstruction within 6 months before the screening period;
- •Other circumstances that the investigator deemed inappropriate for participation in the trial.
研究组 & 干预措施
Study treatment
Participants received BL-B01D1, SI-B003 or BL-B01D1 + SI-B003 therapy 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)
Study treatment
Participants received BL-B01D1, SI-B003 or BL-B01D1 + SI-B003 therapy 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)
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
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Progression-free survival (PFS)(Up to approximately 24 months)
- Disease control rate (DCR)(Up to approximately 24 months)
- Duration of response (DOR)(Up to approximately 24 months)