AdvanTIG-205: A Phase 2, Randomized Study of Ociperlimab (BGB-A1217) and Tislelizumab With Chemotherapy in Patients With Previously Untreated Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 272
- 试验地点
- 64
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
This study aimed to evaluate the safety and effectiveness of ociperlimab combined with tislelizumab and chemotherapy, compared to tislelizumab and chemotherapy alone, in participants with non-small cell lung cancer (NSCLC) that was locally advanced, could not be removed by surgery, or had spread to other parts of the body.
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
- Double (Participant, Investigator)
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
- •Participants had histologically or cytologically confirmed locally advanced or recurrent non-small cell lung cancer (NSCLC) that was not eligible for curative surgical resection and/or definitive radiotherapy, with or without chemotherapy. Alternatively, participants had metastatic non-squamous or squamous NSCLC.
- •Participants had not received any prior systemic therapy for locally advanced or metastatic squamous or non-squamous NSCLC, including but not limited to chemotherapy or targeted therapies. Those who had previously received neoadjuvant or adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease, were required to have experienced a disease-free interval of at least 6 months from the last dose of chemotherapy and/or concurrent radiotherapy prior to randomization.
- •Archival tumor tissue or a fresh biopsy (if archival tissue was unavailable) was required for programmed death-ligand 1 (PD-L1) level assessment and retrospective biomarker analyses. Only participants with evaluable PD-L1 results were considered eligible.
- •Participants were required to have had at least one measurable lesion as assessed by the investigator in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Participants had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
排除标准
- •Participants were excluded if they had known mutations in any of the following genes:
- •Epidermal Growth Factor Receptor (EGFR): For participants with non-squamous NSCLC and unknown EGFR mutation status, tissue-based EGFR testing (performed either locally or at a central laboratory) or an endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)-based EGFR test was required prior to enrollment. Those found to harbor EGFR-sensitizing mutations were excluded.
- •Anaplastic Lymphoma Kinase (ALK) fusion oncogene.
- •B-Raf Proto-Oncogene (BRAF) V600E mutation.
- •ROS Proto-Oncogene 1 (ROS1) rearrangement.
- •Participants who had received prior treatment with EGFR inhibitors, ALK inhibitors, or other targeted therapies for known driver mutations.
- •Participants who had received any prior therapies targeting T-cell costimulatory or checkpoint pathways (e.g., programmed cell death protein 1 [PD-1], programmed death-ligand 1 [PD-L1], or cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]) for metastatic NSCLC were excluded.
- •Participants who had any condition requiring systemic treatment with corticosteroids at a dose greater than 10 mg of prednisone (or equivalent) daily, or other immunosuppressive medications within 14 days prior to randomization.
- •Participants who had an active infection, including but not limited to tuberculosis, requiring systemic antibacterial, antifungal, or antiviral treatment within 14 days prior to randomization were excluded.
- •Note: Additional protocol-defined inclusion and exclusion criteria may have applied.
研究组 & 干预措施
Arm A (O+T+C)
During the induction phase, participants received ociperlimab (O) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (on Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received O 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received O 900 mg IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Ociperlimab (Drug)
Arm A (O+T+C)
During the induction phase, participants received ociperlimab (O) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (on Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received O 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received O 900 mg IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Tislelizumab (Drug)
Arm A (O+T+C)
During the induction phase, participants received ociperlimab (O) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (on Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received O 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received O 900 mg IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Carboplatin (Drug)
Arm A (O+T+C)
During the induction phase, participants received ociperlimab (O) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (on Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received O 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received O 900 mg IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Paclitaxel (Drug)
Arm A (O+T+C)
During the induction phase, participants received ociperlimab (O) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (on Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received O 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received O 900 mg IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Nab paclitaxel (Drug)
Arm A (O+T+C)
During the induction phase, participants received ociperlimab (O) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (on Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received O 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received O 900 mg IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Cisplatin (Drug)
Arm A (O+T+C)
During the induction phase, participants received ociperlimab (O) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (on Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received O 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received O 900 mg IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Pemetrexed (Drug)
Arm B (P+T+C)
During the induction phase, participants received placebo (P) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received placebo 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received placebo IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Tislelizumab (Drug)
Arm B (P+T+C)
During the induction phase, participants received placebo (P) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received placebo 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received placebo IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Carboplatin (Drug)
Arm B (P+T+C)
During the induction phase, participants received placebo (P) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received placebo 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received placebo IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Paclitaxel (Drug)
Arm B (P+T+C)
During the induction phase, participants received placebo (P) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received placebo 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received placebo IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Nab paclitaxel (Drug)
Arm B (P+T+C)
During the induction phase, participants received placebo (P) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received placebo 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received placebo IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Cisplatin (Drug)
Arm B (P+T+C)
During the induction phase, participants received placebo (P) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received placebo 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received placebo IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Pemetrexed (Drug)
Arm B (P+T+C)
During the induction phase, participants received placebo (P) 900 mg IV, tislelizumab (T) 200 mg IV, and histology-based chemotherapy (C) every 21 days for 4-6 cycles. For squamous NSCLC, chemotherapy included carboplatin AUC 5 or 6 (Day 1) + paclitaxel 175 or 200 mg/m² (Day 1) or nab-paclitaxel 100 mg/m² (Days 1, 8, 15) every 3 weeks. For non-squamous NSCLC, chemotherapy included cisplatin 75 mg/m² or carboplatin AUC 5 (Day 1) + pemetrexed (P) 500 mg/m² IV (Day 1), every 3 weeks.
In the maintenance phase, non-squamous NSCLC participants received placebo 900 mg IV, T 200 mg IV, and pemetrexed 500 mg/m² IV every 3 weeks. Squamous NSCLC participants received placebo IV and T 200 mg IV every 3 weeks until toxicity, consent withdrawal, or investigator-determined lack of benefit.
干预措施: Placebo (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months
PFS was defined as the time from randomization to the first objectively documented disease progression as assessed by the investigator per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) or death from any cause, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.
次要结局
- Objective Response Rate (ORR)(From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months)
- Duration of Response (DOR)(From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months)
- Overall Survival (OS)(From randomization up to the final efficacy analysis data cut-off date of 04 September 2024; Up to 33 months)
- Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From first dose of study drug to 30 days after last dose, up to the study completion date cut-off date of 04 September 2024 (up to 32.4 months))