AdvanTIG-306: A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Ociperlimab (WCD118/BGB-A1217) Combined With Tislelizumab (VDT482/BGB-A317) Plus Platinum-based Doublet Chemotherapy Versus Placebo Combined With Pembrolizumab Plus Platinum-based Doublet Chemotherapy as First-line Therapy for Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 主要终点
- Progression-free survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment as per RECIST 1.1 in participants with PD-L1 expression in ≥1% of tumor cells (Arm A and B)
研究概览
简要总结
The primary scientific question of interest is whether the addition of ociperlimab to platinum-based chemotherapy and tislelizumab improve progression-free survival (PFS) or overall survival (OS) compared to pembrolizumab and platinum-based chemotherapy as first-line therapy for participants with locally advanced or metastatic squamous or non-squamous NSCLC with PD-L1 expression of ≥1%.
详细描述
This is a randomized, double-blind, placebo controlled, multicenter, phase III study evaluating the efficacy and safety of ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy as first-line treatment for participants with locally advanced or metastatic NSCLC without actionable driver mutations.
Participants will receive study treatment every three weeks and will continue to receive it until RECIST 1.1 disease progression as determined by Investigator and confirmed by BIRC, unacceptable toxicity that precludes further treatment, treatment is discontinued at the discretion of the Investigator or participant, participant withdrawal of consent, pregnancy, lost to follow-up, or death.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for definitive chemoradiation, radiation or surgery) or metastatic (stage IV) NSCLC (according to AJCC: Cancer Staging Manual, 8th edition) participants with no previous systemic treatment for advanced disease.
- •Known PD-L1 status determined, prior to study randomization
- •At least one measurable lesion as defined by RECIST 1.1 according to local radiology assessment at screening.
- •ECOG performance status ≤
排除标准
- •Active autoimmune diseases requiring treatment with steroids or immunosuppressors in the past 2 years prior to randomization.
- •History of severe hypersensitivity reaction or any contraindication to ociperlimab, tislelizumab, pembrolizumab (or any other monoclonal antibodies), platinum containing drugs, nab-paclitaxel, paclitaxel, pemetrexed or any known excipients of these drugs.
- •Participants with known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Participants with documented epidermal growth factor receptor (EGFR) sensitizing mutations, and/or ALK rearrangement assessed as part of the patients's standard of care by a validated test, as per local regulations will be excluded from the study.
- •Participants with other known druggable molecular drivers (any histology) such as BRAF V600, KRASG12C, MET exon 14 mutations, NTRK, RET or ROS-1 rearrangement diagnosed per local tests who might be candidates for alternative targeted therapies as applicable per local regulations and treatment guidelines are excluded.
- •Other inclusion/exclusion criteria may apply
研究组 & 干预措施
Arm A: Ociperlimab + tislelizumab + chemotherapy
Participants will receive ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Ociperlimab (Drug)
Arm A: Ociperlimab + tislelizumab + chemotherapy
Participants will receive ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Tislelizumab (Drug)
Arm A: Ociperlimab + tislelizumab + chemotherapy
Participants will receive ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Carboplatin (Drug)
Arm A: Ociperlimab + tislelizumab + chemotherapy
Participants will receive ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Cisplatin (Drug)
Arm A: Ociperlimab + tislelizumab + chemotherapy
Participants will receive ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Pemetrexed (Drug)
Arm A: Ociperlimab + tislelizumab + chemotherapy
Participants will receive ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Paclitaxel (Drug)
Arm A: Ociperlimab + tislelizumab + chemotherapy
Participants will receive ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Nab-paclitaxel (Drug)
Arm B: Placebo + pembrolizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
干预措施: Placebo (Drug)
Arm B: Placebo + pembrolizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
干预措施: Pembrolizumab (Drug)
Arm B: Placebo + pembrolizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
干预措施: Carboplatin (Drug)
Arm B: Placebo + pembrolizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
干预措施: Cisplatin (Drug)
Arm B: Placebo + pembrolizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
干预措施: Pemetrexed (Drug)
Arm B: Placebo + pembrolizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
干预措施: Paclitaxel (Drug)
Arm B: Placebo + pembrolizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
干预措施: Nab-paclitaxel (Drug)
Arm C: Placebo + tislelizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Placebo (Drug)
Arm C: Placebo + tislelizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Tislelizumab (Drug)
Arm C: Placebo + tislelizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Carboplatin (Drug)
Arm C: Placebo + tislelizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Cisplatin (Drug)
Arm C: Placebo + tislelizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Pemetrexed (Drug)
Arm C: Placebo + tislelizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Paclitaxel (Drug)
Arm C: Placebo + tislelizumab + chemotherapy
Participants will receive ociperlimab placebo in combination with tislelizumab and platinum-based doublet chemotherapy
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Progression-free survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment as per RECIST 1.1 in participants with PD-L1 expression in ≥1% of tumor cells (Arm A and B)
时间窗: Up to 30 months
Time from date of randomization/start of treatment to the date of event defined as the first documented progression based on BIRC assessment as per RECIST 1.1 or death due to any cause in participants with PD-L1 expression in ≥1% of tumor cells, for participants in Arm A compared to Arm B
Overall survival (OS) in participants with PD-L1 expression in ≥1% of tumor cells (Arm A and B)
时间窗: Up to 52 months
Time from date of randomization/start of treatment to date of death due to any cause in participants with PD-L1 expression in ≥1% of tumor cells, for participants in Arm A compared to Arm B
次要结局
- OS in all participants regardless of PD-L1 status (Arm A and B)(Up to 52 months)
- Time to definitive 10-point deterioration in symptom scores for chest pain, cough and dyspnea on the EORTC QLQ-LC13 questionnaire(Up to 30 months)
- PFS based on BIRC assessment as per RECIST 1.1 in all participants regardless of PD-L1 status (Arm A and B)(Up to 30 months)
- Time to response (TTR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)(Up to 30 months)
- Pharmacokinetic (PK) parameter: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of ociperlimab and tislelizumab(Up to 30 months)
- Time to confirmed 10-point deterioration in symptom scores for chest pain, cough and dyspnea on the EORTC QLQ-LC13 questionnaire(Up to 30 months)
- PFS based on BIRC assessment as per RECIST 1.1 (Arm A and C)(Up to 30 months)
- PK parameter: AUC calculated at the end of the dosing interval (AUCtau)of ociperlimab and tislelizumab(Up to 30 months)
- Immunogenicity: Anti-drug antibodies (ADA) prevalence at baseline of ociperlimab and tislelizumab(Baseline)
- Overall response rate (ORR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)(Up to 30 months)
- Duration of response (DOR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)(Up to 30 months)
- ORR based in BIRC assessment as per RECIST 1.1 (Arm A and C)(Up to 30 months)
- DCR based in BIRC assessment as per RECIST 1.1 (Arm A and C)(Up to 30 months)
- TTR based in BIRC assessment as per RECIST 1.1 (Arm A and C)(Up to 30 months)
- DOR based in BIRC assessment as per RECIST 1.1 (Arm A and C)(Up to 30 months)
- PK parameter: Time to reach maximum concentration (Tmax) of ociperlimab and tislelizumab(Up to 30 months)
- PK parameter: Lowest serum concentration reached before the next dose is administered (Ctrough) of ociperlimab and tislelizumab(Up to 30 months)
- Immunogenicity: ADA incidence following treatment with ociperlimab and tislelizumab(Up to 30 months)
- Disease Control Rate (DCR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)(Up to 30 months)
- PK parameter: Maximum concentration (Cmax) of ociperlimab and tislelizumab(Up to 30 months)
- Progression-free survival deferred (PFS2)(Up to 30 months)
- Time to definitive 10-point deterioration in physical and role functioning on the EORTC QLQ-C30 questionnaire(Up to 30 months)
- Time to confirmed 10-point deterioration in physical and role functioning on the EORTC QLQ-C30 questionnaire(Up to 30 months)
- Time to definitive 10-point deterioration in global health status/quality of life, shortness of breath and pain on the EORTC QLQ-C30 questionnaire(Up to 30 months)
- Utility scores of the EQ-5D-5L(Up to 30 months)
- Time to definitive deterioration of the ECOG performance status(Up to 30 months)