A Randomized, Open-label, Multicenter Phase II/III Clinical Study Evaluating BL-B01D1 in Combination With a PD-1/VEGF Bispecific Antibody Versus Tislelizumab Plus Platinum-doublet Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer(PANKU-Lung06)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Phase II: Objective Response Rate (ORR)
研究概览
简要总结
This trial is a registrational randomized, open-label, multicenter Phase II/III study designed to evaluate the efficacy and safety of BL-B01D1 in combination with a PD-1/VEGF bispecific antibody in patients with locally advanced or metastatic non-squamous non-small cell lung cancer.
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 non-squamous non-small cell lung cancer;
- •Agree to provide tumor tissue samples obtained at or after diagnosis of locally advanced or metastatic cancer;
- •Must have at least one measurable lesion as defined by RECIST v1.1;
- •ECOG performance status score of 0 or 1;
- •Toxicities from prior anti-tumor therapy 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 required criteria;
- •Urinary protein ≤ 2+ or < 1000 mg/24h;
- •For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment; serum pregnancy test must rule out pregnancy; patients must be non-lactating and must use highly effective contraceptive measures throughout the treatment period and for 7 months after the last dose. For male participants whose partners are women of childbearing potential, adequate barrier contraceptive measures must be used throughout the treatment period and for 7 months after the end of treatment.
排除标准
- •Presence of small cell lung cancer, neuroendocrine carcinoma, sarcomatoid carcinoma components, or squamous carcinoma components exceeding 10%;
- •Evidence suggesting the presence of EGFR-sensitive mutations, etc.;
- •Patients who have received prior systemic therapy;
- •Prior receipt of therapies targeting the mechanism of tumor immunity;
- •Prior receipt of antibody-drug conjugates (ADCs) using topoisomerase I inhibitors as the toxin, etc.;
- •Trial participants who have received prior systemic anti-angiogenic therapy;
- •Receipt of radical radiotherapy, major surgery, or large-field radiotherapy within 4 weeks before study randomization;
- •History of severe cardiac or cerebrovascular disease;
- •Receiving long-term systemic corticosteroid therapy (e.g., >10 mg/day prednisone) prior to the first dose;
- •Active autoimmune diseases and inflammatory diseases;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months before screening;
- •Prolonged QT interval, complete left bundle branch block, etc.;
- •Diagnosis of active malignancy within 3 years before study randomization;
- •Hypertension poorly controlled by two antihypertensive medications;
- •Patients with poorly controlled blood glucose;
- •History of ILD requiring steroid therapy, current ILD, or ≥ grade 2 radiation pneumonitis, etc.;
- •Concurrent pulmonary diseases resulting in clinically severe impairment of respiratory function;
- •Patients with active central nervous system metastases;
- •Occurrence of severe infection within 4 weeks before study randomization;
- •Presence of large serous cavity effusions, or symptomatic serous cavity effusions, etc.;
- •Imaging findings suggesting tumor invasion or encasement of abdominal, thoracic, or other regions;
- •Presence of serious non-healing wounds, ulcers, or fractures within 4 weeks before signing informed consent;
- •Trial participants with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing informed consent;
- •Patients with a history of inflammatory bowel disease, extensive bowel resection, immune-mediated enteritis, intestinal obstruction, or chronic diarrhea, etc.;
- •History of allergy to recombinant humanized antibodies or allergy to the investigational drug, etc.;
- •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 investigational drugs or treatments within 4 weeks before study randomization;
- •Trial participants who plan to receive or have received live vaccines within 28 days before study randomization;
- •Other conditions that, in the investigator's opinion, make the patient unsuitable for participation in this clinical trial due to complications or other circumstances.
研究组 & 干预措施
Tislelizumab + Pemetrexed + Carboplatin or Cisplatin
Participants receive Tislelizumab + Pemetrexed + Carboplatin or Cisplatin 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)
PD-1/VEGF Bispecific Antibody + Pemetrexed + Carboplatin or Cisplatin
Participants receive PD-1/VEGF Bispecific Antibody + Pemetrexed + Carboplatin or Cisplatin 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: Cisplatin (Drug)
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)
Tislelizumab + Pemetrexed + Carboplatin or Cisplatin
Participants receive Tislelizumab + Pemetrexed + Carboplatin or Cisplatin 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: Tislelizumab (Drug)
Tislelizumab + Pemetrexed + Carboplatin or Cisplatin
Participants receive Tislelizumab + Pemetrexed + Carboplatin or Cisplatin 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: Pemetrexed (Drug)
PD-1/VEGF Bispecific Antibody + Pemetrexed + Carboplatin or Cisplatin
Participants receive PD-1/VEGF Bispecific Antibody + Pemetrexed + Carboplatin or Cisplatin 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: Pemetrexed (Drug)
Tislelizumab + Pemetrexed + Carboplatin or Cisplatin
Participants receive Tislelizumab + Pemetrexed + Carboplatin or Cisplatin 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: Cisplatin (Drug)
PD-1/VEGF Bispecific Antibody + Pemetrexed + Carboplatin or Cisplatin
Participants receive PD-1/VEGF Bispecific Antibody + Pemetrexed + Carboplatin or Cisplatin 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)
结局指标
主要结局
Phase II: 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.
Phase III: Overall Survival (OS)
时间窗: Up to approximately 24 months
Overall survival (OS) is defined as the time between the day the subject is randomized and the subject's death.
次要结局
- 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: Treatment Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Phase III: Progression-free Survival (PFS)(Up to approximately 24 months)
- Phase III: BICR and Investigator-assessed Objective Response Rate (ORR)(Up to approximately 24 months)
- Phase III: Cmax(Up to approximately 24 months)
- Phase III: Tmax(Up to approximately 24 months)
- Phase III: T1/2(Up to approximately 24 months)
- Phase III: AUC0-t(Up to approximately 24 months)
- Phase III: CL (Clearance)(Up to approximately 24 months)
- Phase III: Ctrough(Up to approximately 24 months)
- Phase III: Anti-drug Antibody (ADA)(Up to approximately 24 months)
- Phase III: Neutralizing Antibody(NAb)(Up to approximately 24 months)