An Open-Label, Multi-Drug, Multi-Centre, Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumour Activity of Novel Combinations in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (LIBRA)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 278
- 试验地点
- 83
- 主要终点
- Number of participants with adverse events (AE) and serious adverse events (SAE)
研究概览
简要总结
This is a Phase II, multi-center, open-label platform study evaluating novel combination treatment options in participants with locally advanced or metastatic NSCLC. The study will consist of several sub-studies, each evaluating the safety, tolerability, and preliminary antitumour activity of various treatment combinations. This study will be conducted in approximately 80 centers globally across 10 countries.
详细描述
The master protocol will include 3 sub-studies, each focused on a specific disease population.
- Sub-study 1 will investigate rilvegostomig± ramucirumab in 1L non-actionable genomic alterations (AGA) NSCLC with PD-L1 ≥50%.
- Sub-study 2 will investigate rilvegostomig + ramucirumab in 1L non-actionable genomic alterations (AGA) NSCLC with PD-L1 1-49%.
- Sub-study 3 will investigate Dato-DXd + ramucirumab ± rilvegostomig in 2/3L AGA+
Each sub-study may include 2 parts (unless stated in the individual sub study protocols): Part A: one or more Safety Run-in cohort(s), and Part B: one or more Dose Expansion cohort(s).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •for All Sub-studies:
- •Participant must be ≥ 18 years of age at the time of signing the ICF
- •WHO/ECOG performance status of 0 or 1
- •At least 1 lesion that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline.
- •Adequate bone marrow and organ function
- •Life expectancy ≥ 12 weeks
- •Provision of acceptable tumour tissue
- •Specific Inclusion Criteria for Sub-Study 1 and Sub-Study 2:
- •Histologically or cytologically documented advanced or metastatic NSCLC
- •PD-L1 TC ≥ 1% (TC≥ 50% for sub-study 1, 1-49% for sub-study 2)
- •Absence of sensitizing EGFR mutations or ALK rearrangements. No known other Actionable Genomic Alterations(AGAs)
- •Specific Inclusion Criteria for Sub-Study 3:
- •Histologically or cytologically documented advanced or metastatic non-squamous NSCLC
- •Documented positive AGA and had progressed on prior targeted therapy
排除标准
- •for All Sub-studies:
- •As judged by the investigator, any severe or uncontrolled systemic diseases, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol
- •Active or prior documented autoimmune or inflammatory disorders
- •Persistent toxicities (CTCAE Grade ≥ 2) (NCI CTCAE v5.0) caused by previous anti cancer therapy, excluding alopecia.
- •Spinal cord compression or leptomeningeal carcinomatosis for sub-study 1 and sub-study
- •Unstable spinal cord compression for sub-study 3
- •Unstable brain metastases
- •History of another primary malignancy.
- •Active infection, including TB and infections with HIV, HBV (verified by known positive HBsAg result), HCV.
- •Uncontrolled or significant cardiac disease
- •Receipt of prior systemic chemotherapy/chemoradiation/immunotherapy for advanced NSCLC for sub-study 1 and sub-study
- •Prior exposure to immune-mediated therapy
- •History of uncontrolled hypertension, and active bleeding diseases, and high risks of bleeding and disorders of coagulation
- •Any concurrent anti-cancer treatment.
- •Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention.
研究组 & 干预措施
Sub-study 1, investigate rilvegostomig± ramucirumab in 1L non-AGA NSCLC with PD-L1 ≥50%
Participants will receive rilvegostomig ± ramucirumab until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion
干预措施: Rilvegostomig (Drug)
Sub-study 1, investigate rilvegostomig± ramucirumab in 1L non-AGA NSCLC with PD-L1 ≥50%
Participants will receive rilvegostomig ± ramucirumab until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion
干预措施: Ramucirumab (Drug)
Sub-study 2, investigate rilvegostomig + ramucirumab in 1L non-AGA NSCLC with PD-L1 1-49%
Participants will receive rilvegostomig + ramucirumab until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion
干预措施: Rilvegostomig (Drug)
Sub-study 2, investigate rilvegostomig + ramucirumab in 1L non-AGA NSCLC with PD-L1 1-49%
Participants will receive rilvegostomig + ramucirumab until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion
干预措施: Ramucirumab (Drug)
Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2/3L AGA+ NSCLC
Participants will receive Dato-DXd + ramucirumab ± rilvegostomig until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion
干预措施: Dato-DXd (Drug)
Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2/3L AGA+ NSCLC
Participants will receive Dato-DXd + ramucirumab ± rilvegostomig until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion
干预措施: Ramucirumab (Drug)
Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2/3L AGA+ NSCLC
Participants will receive Dato-DXd + ramucirumab ± rilvegostomig until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion
干预措施: Rilvegostomig (Drug)
结局指标
主要结局
Number of participants with adverse events (AE) and serious adverse events (SAE)
时间窗: Through study completion, an average of 3 years
To assess the safety and tolerability
Objective response rate (ORR)
时间窗: Through study completion, an average of 3 years
ORR is defined as the proportion of participants who have a confirmed CR (complete response) or confirmed PR (partial response) per RECIST 1.1
次要结局
- Best Overall Response(BOR)(Through study completion, an average of 3 years)
- Change in Target Lesion Tumor Size(Through study completion, an average of 3 years)
- Disease Control Rate(DCR) at 12 Weeks(From Day 1 pre-dose to 12 weeks)
- Duration Of Response (DoR)(Through study completion, an average of 3 years)
- Overall Survival(OS)(Through study completion, an average of 3 years)
- Serum concentration(Through study completion, an average of 3 years)
- Maximum plasma drug concentration (Cmax)(Through study completion, an average of 3 years)
- Immunogenicity of study interventions in participants receiving treatment(Through study completion, an average of 3 years)
- Progression free survival (PFS)(Through study completion, an average of 3 years)