A Phase II/III Clinical Study Comparing BL-B01D1 in Combination With PD-1/VEGF Bispecific Antibody Versus Chemotherapy in Combination With PD-1/VEGF Bispecific Antibody in First-line Patients With Locally Advanced or Metastatic Squamous Non-small Cell Lung Cancer(PANKU-Lung05)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Phase II: Investigator-assessed Objective Response Rate (ORR)
研究概览
简要总结
This trial is a registrational Phase II/III randomized, open-label, multicenter study designed to evaluate the efficacy and safety of BL-B01D1 in combination with PD-1/VEGF bispecific antibody in first-line patients with locally advanced or metastatic squamous non-small cell lung cancer.
详细描述
The entire study consists of two stages, Phase II and Phase III, both of which are randomized, open-label studies.
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 form and comply with the protocol requirements;
- •Age ≥18 years;
- •Expected survival time ≥3 months;
- •Patients with locally advanced or metastatic squamous non-small cell lung cancer;
- •Agree to provide tumor tissue samples obtained at or after the diagnosis of locally advanced or metastatic disease;
- •Must have at least one measurable lesion as defined by RECIST v1.1;
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
- •Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
- •No severe cardiac dysfunction, with left ventricular ejection fraction ≥50%;
- •Organ function levels must meet the specified requirements;
- •Urinary protein ≤1+ or <1000 mg/24h;
- •For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, with serum pregnancy test excluding pregnancy, and patients must be non-lactating; all enrolled patients (regardless of male or female) must take adequate barrier contraceptive measures throughout the entire treatment period and for 7 months after the end of treatment.
排除标准
- •Prior histological or cytological evidence of small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma components;
- •Indications of the presence of EGFR-sensitive mutations, among others;
- •Patients who have received prior systemic therapy;
- •Prior treatment with agents targeting the mechanism of tumor immune action;
- •Prior treatment with ADC drugs that use topoisomerase I inhibitors as the toxin, among others;
- •Receipt of radical radiotherapy, major surgery, or large-field radiotherapy within 4 weeks before study randomization;
- •History of severe heart disease or cerebrovascular disease;
- •Receipt of long-term systemic corticosteroid therapy (e.g., prednisone >10 mg/day) before the first dose;
- •Active autoimmune diseases and inflammatory diseases requiring systemic treatment within 2 years;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months before screening;
- •Prolonged QTc interval, complete left bundle branch block, among others;
- •Diagnosis of active malignancy within 3 years before study randomization;
- •Hypertension inadequately controlled by two antihypertensive medications;
- •Patients with poorly controlled blood glucose levels;
- •History of ILD requiring steroid therapy, current ILD, or grade ≥2 radiation pneumonitis, among others;
- •Pulmonary diseases leading to clinically severe impairment of respiratory function;
- •Patients with active central nervous system metastases;
- •Severe infection occurring within 4 weeks before study randomization;
- •Presence of large serous cavity effusions or symptomatic serous cavity effusions, among others;
- •Imaging findings indicating tumor invasion or encasement of the abdomen, chest, etc.;
- •Severe non-healing wounds, ulcers, or fractures within 4 weeks before signing informed consent;
- •Trial participants with clinically significant bleeding or a significant bleeding tendency within 4 weeks prior to signing informed consent;
- •Patients with inflammatory bowel disease, history of extensive bowel resection, history of immune enteritis, intestinal obstruction, or chronic diarrhea, among others;
- •History of allergy to recombinant humanized antibodies or hypersensitivity to any excipient of BL-B01D1;
- •History of autologous or allogeneic stem cell transplantation;
- •Positive for human immunodeficiency virus antibody, active hepatitis B virus infection, or hepatitis C virus infection;
- •History of severe neurological or psychiatric disorders;
- •Receipt of other unapproved clinical study drugs or treatments within 4 weeks before study randomization;
- •Trial participants planning to receive or having received live vaccines within 28 days before study randomization;
- •Other conditions deemed by the investigator as unsuitable for participation in this clinical trial due to complications or other circumstances.
研究组 & 干预措施
BL-B01D1 + PD-1/VEGF bispecific antibody
Participants receive BL-B01D1 + PD-1/VEGF bispecific antibody 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: BL-B01D1 (Drug)
Paclitaxel + Carboplatin + PD-1/VEGF bispecific antibody
Participants receive Paclitaxel + Carboplatin + PD-1/VEGF bispecific antibody 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: Carboplatin (Drug)
Paclitaxel + Carboplatin + PD-1/VEGF bispecific antibody
Participants receive Paclitaxel + Carboplatin + PD-1/VEGF bispecific antibody 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
Phase II: Investigator-assessed Objective Response Rate (ORR)
时间窗: Up to approximately 24 months
Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS).
Phase II: Investigator-assessed Progression-free Survival (PFS)
时间窗: Up to approximately 24 months
Investigator-assessed progression-free survival (PFS) per RECIST v1.1 is defined as the time from treatment initiation until the first documented disease progression according to RECIST v1.1 criteria, or death from any cause, whichever occurs first, as determined by the local treating investigator.
Phase III: BICR-assessed Progression-free Survival (PFS)
时间窗: Up to approximately 24 months
Progression-free survival (PFS) as assessed by BICR is defined as the time between the date subjects were randomized and the first observation of disease progression (based on BICR's image-based assessment) or death.
次要结局
- Phase II/III:Treatment Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Phase II/III: Progression-free Survival (PFS)(Up to approximately 24 months)
- Phase II/III: Objective Response Rate (ORR)(Up to approximately 24 months)
- Phase II/III: Disease Control Rate (DCR)(Up to approximately 24 months)
- Phase II/III: Duration of Response (DOR)(Up to approximately 24 months)
- Phase II/III: Cmax(Up to approximately 24 months)
- Phase II/III: Tmax(Up to approximately 24 months)
- Phase II/III: T1/2(Up to approximately 24 months)
- Phase II/III: AUC0-t(Up to approximately 24 months)
- Phase II/III: CL (Clearance)(Up to approximately 24 months)
- Phase II/III: Ctrough(Up to approximately 24 months)
- Phase II/III: Anti-drug Antibody (ADA)(Up to approximately 24 months)
- Phase II/III: Neutralizing Antibody(NAb)(Up to approximately 24 months)
- Phase II: Drug-Drug Interaction (DDI)(Up to approximately 24 months)
- Phase III: Overall Survival (OS)(Up to approximately 24 months)