A Phase 3, Randomized, Open-Label Study to Compare Ociperlimab (BGB-A1217) Plus Tislelizumab (BGB-A317) Versus Durvalumab in Patients With Locally Advanced, Unresectable, PD-L1-Selected Non-Small Cell Lung Cancer Whose Disease Has Not Progressed After Concurrent Chemoradiotherapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 63
- 试验地点
- 32
- 主要终点
- Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)
研究概览
简要总结
The purpose of this study was to evaluate the safety and efficacy of ociperlimab in combination with tislelizumab compared to durvalumab in adults with stage III unresectable PD-L1-selected non-small cell lung cancer whose disease has not progressed after cCRT.
详细描述
The study initiated with Protocol Amendment 1.0 (PA 1; dated on 16 April 2021). In April 2022 Protocol Amendment 2 (PA 2) was implemented. In PA 1, participants with newly diagnosed, histologically confirmed, unresectable locally advanced NSCLC and evaluable PD-L1 expression all comers were enrolled; cCRT was given within the study. In PA 2, the enrollment of the target population was revised into participants with unresectable locally advanced NSCLC whose disease has not progressed after definitive, platinum-based cCRT and with PD-L1 expression on ≥ 1% of tumor cells as assessed by the central lab; cCRT was given outside of the study.
After implementation of PA 2, participants who were randomized under PA 1 were given the option to continue assigned study treatment or to discontinue assigned treatment and begin standard of care treatment outside of the study. Participants enrolled under PA 1 were excluded from the primary and secondary analysis specified by PA 2.
This study was subsequently terminated by the Sponsor prior to enrollment of any participants under PA 2.
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
- •Age ≥ 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place).
- •Participant has histologically or cytologically confirmed, locally advanced, unresectable Stage III NSCLC (AJCC Cancer Staging Manual 2017, derived from IASLC) prior to initiation of cCRT.
- •Participant must have completed at least 2 cycles of platinum-based chemotherapy concurrent with radiotherapy
- •Participants must have not experienced PD following definitive, platinum-based cCRT.
- •Eastern Co-operative Oncology Group (ECOG) Performance Status of 0 or
- •Participants must have adequate organ function
- •Agree to provide archival tissue (formalin-fixed paraffin-embedded block containing tumor [preferred] or approximately 6 to 15 freshly cut unstained slides) or fresh biopsy obtained prior to cCRT (if archival tissue is not available) for prospective central evaluation of PD-L1 levels and retrospective analysis of other biomarkers.
排除标准
- •Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT, or any other antibody or drugs specifically targeting T-cell co-stimulation or checkpoint pathways.
- •Diagnosed with NSCLC that harbors an epidermal growth factor receptor (EGFR) sensitizing mutation, anaplastic lymphoma kinase (ALK) gene translocation, ROS1 gene translocation or RET gene rearrangement.
- •Participants who received systemic anticancer treatment besides the specified cCRT.
- •Any unresolved toxicity CTCAE > Grade 2 from the prior cCRT.
- •Active autoimmune diseases or history of autoimmune diseases that may relapse.
- •Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone [in Japan, prednisolone] or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study treatment.
- •Infection (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days before the first dose of study treatment.
- •Note: Antiviral therapy is permitted for participants with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- •NOTE: Other protocol Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Ociperlimab + Tislelizumab + cCRT
Participants enrolled under PA1 recieved two cycles of ociperlimab combined with tislelizumab and cCRT, followed by ociperlimab combined with tislelizumab up to 1 year after the cCRT phase
干预措施: Tislelizumab (Drug)
Ociperlimab + Tislelizumab + cCRT
Participants enrolled under PA1 recieved two cycles of ociperlimab combined with tislelizumab and cCRT, followed by ociperlimab combined with tislelizumab up to 1 year after the cCRT phase
干预措施: Ociperlimab (Drug)
Ociperlimab + Tislelizumab + cCRT
Participants enrolled under PA1 recieved two cycles of ociperlimab combined with tislelizumab and cCRT, followed by ociperlimab combined with tislelizumab up to 1 year after the cCRT phase
干预措施: Chemotherapy (Drug)
Ociperlimab + Tislelizumab + cCRT
Participants enrolled under PA1 recieved two cycles of ociperlimab combined with tislelizumab and cCRT, followed by ociperlimab combined with tislelizumab up to 1 year after the cCRT phase
干预措施: Radiotherapy (Radiation)
Tislelizumab + cCRT
Participants enrolled under PA1 recieved two cycles of tislelizumab combined with cCRT, followed by tislelizumab up to 1 year after the cCRT phase
干预措施: Tislelizumab (Drug)
Tislelizumab + cCRT
Participants enrolled under PA1 recieved two cycles of tislelizumab combined with cCRT, followed by tislelizumab up to 1 year after the cCRT phase
干预措施: Chemotherapy (Drug)
Tislelizumab + cCRT
Participants enrolled under PA1 recieved two cycles of tislelizumab combined with cCRT, followed by tislelizumab up to 1 year after the cCRT phase
干预措施: Radiotherapy (Radiation)
cCRT followed by Durvalumab
Participants enrolled under PA1 recieved two cycles of cCRT, followed by durvalumab to 1 year after the cCRT phase
干预措施: Durvalumab (Drug)
cCRT followed by Durvalumab
Participants enrolled under PA1 recieved two cycles of cCRT, followed by durvalumab to 1 year after the cCRT phase
干预措施: Chemotherapy (Drug)
cCRT followed by Durvalumab
Participants enrolled under PA1 recieved two cycles of cCRT, followed by durvalumab to 1 year after the cCRT phase
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)
时间窗: From randomization through to the end of study, planned duration was 20 months
PFS is defined as the time from the date of randomization to the date of first documentation of disease progression as assessed by the IRC per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or death, whichever occurred first.
次要结局
- Overall Survival (OS)(From randomization through to the end of study, planned duration was 20 months)
- Overall Response Rate (ORR)(From randomization through to the end of study, planned duration was 20 months)
- Duration of Response (DOR)(From randomization through to the end of study, planned duration was 20 months)
- Time to Death or Distant Metastasis (TTDM) as Assessed by the Investigator(From randomization through to the end of study, planned duration was 20 months)
- Progression-Free Survival 2 (PFS2)(From randomization through to the end of study, planned duration was 20 months)
- Number of Participants Experiencing Adverse Events (AEs)(From first dose to 30 days after the last dose or initiation of a new anticancer therapy, whichever occured first; through study completion data cut-off date of October 17th, 2023 (maximum time on treatment was 16 months))
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status(Baseline and Cycle 6 (Each cycle is 21 days))
- Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)(Baseline and Cycle 6 (Each cycle is 21 days))
- Change From Baseline in Health Related Quality of Life (HRQoL) as Assessed by European Quality of Life-5 Dimensions (EQ-5D-5L)(Baseline and Cycle 6 (Each cycle is 21 days))
- Serum Concentration of Ociperlimab(Predose at Day 1 of Cycles 1, 2, 5, 9, and 17; postdose on Day 1 of Cycles 1, 5 and EOT visit (Each Cycle was 21 days))
- Serum Concentration of Tislelizumab for Participants in the Ociperlimab + Tislelizumab + cCRT Treatment Group(Predose at Day 1 of Cycles 1, 2, 5, 9, 17; postdose on Day 1 of Cycles 1 and 5, and EOT visit (each cycle was 21 days))
- Serum Concentration of Tislelizumab for Participants in the Tislelizumab + cCRT Treatment Group(Predose at Day 1 of Cycles 1, 2, 5, 9, and 17; postdose on Day 1 of Cycles 1 and 5, and EOT visit (Each Cycle is 21 days))
- Immunogenic Responses to Ociperlimab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs)(Predose (within 60 minutes before dose) on Day 1 of Cycles 1, 2, 5, 9, 17, and the EOT Visit (Each cycle is 21 days). Maximum number of treatment cycles was 19)
- Immunogenic Responses to Tislelizumab as Assessed by the Detection of Treatment Emergent Anti-Drug Antibodies (ADAs)(Predose (within 60 minutes before dose) on Day 1 of Cycles 1, 2, 5, 9, 17, and the EOT Visit (Each cycle is 21 days, maximum number of treatment cycles was 19))
- Programmed Death-Ligand 1 (PD-L1) and T-cell Immunoreceptor With Ig and ITIM Domains (TIGIT) Expression in Archival and/or Fresh Tumor Tissues(From randomization through to the end of study, planned duration was 20 months)