A Phase 1b Study of Venetoclax in Combination With Pembrolizumab in Subjects With Previously Untreated NSCLC Whose Tumors Have High PD-L1 Expression
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 2
- 试验地点
- 39
- 主要终点
- Number of Participants with Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. It is the most common form of lung cancer, accounting for around 85% of lung cancers. The purpose of this study is to evaluate the safety and efficacy (how well the study drug works against the disease) of venetoclax in combination with pembrolizumab in participants with NSCLC.
Venetoclax is a drug that kills cancer cells by blocking a protein (part of a cell) that allows cancer cells to stay alive. Pembrolizumab is approved drug for the treatment of NSCLC. It works with your immune system to help fight certain cancers. The study is split into two portions - dose escalation and randomization. Participants are assigned one of the three treatment groups to receive pembrolizumab alone or in combination with venetoclax. Each group receives a different treatment. Participants who are at least 18 years of age with a diagnosis of NSCLC will be enrolled. Around 100 participants will be enrolled in the study in approximately 44 sites across United States.
Participants will receive intravenous (IV) infusion of pembrolizumab alone or in combination with oral venetoclax tablets.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically documented advanced or metastatic NSCLC with no known epidermal growth factor receptor (EGFR) sensitizing (activating) mutation or anaplastic lymphoma kinase (ALK) translocation.
- •At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.
- •High PD-L1 tumor expression (tumor proportion score >= 50%) as determined by a Food and Drug Administration (FDA)-approved test.
- •Willing to provide tissue biopsy sample prior to start of study.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
排除标准
- •Received prior systemic treatment for their advanced or metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
- •History of or ongoing interstitial lung disease or pneumonitis that required oral or intravenous (IV) steroids.
- •Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If a participant has signs/symptoms suggestive of SARS-CoV-2 infection, they should undergo molecular (e.g., polymerase chain reaction [PCR]) testing to rule out SARS-CoV-2 infection.
研究组 & 干预措施
Dose Escalation Phase: Venetoclax + Pembrolizumab
Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A.
干预措施: Venetoclax (Drug)
Dose Escalation Phase: Venetoclax + Pembrolizumab
Participants will receive escalating doses of venetoclax in combination with pembrolizumab Dose A.
干预措施: Pembrolizumab (Drug)
Randomization Phase: Venetoclax + Pembrolizumab
Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A.
干预措施: Venetoclax (Drug)
Randomization Phase: Venetoclax + Pembrolizumab
Participants will receive venetoclax at dose levels determined in the dose escalation phase in combination with pembrolizumab Dose A.
干预措施: Pembrolizumab (Drug)
Randomization Phase: Pembrolizumab Monotherapy
Participants will receive pembrolizumab Dose A
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Number of Participants with Dose-Limiting Toxicities (DLTs)
时间窗: Up to 28 Days
DLTs are adverse events that are considered to have a reasonable possibility of relationship to the administration of venetoclax and pembrolizumab and cannot be attributed by the investigator to a clearly identifiable cause such as disease progression, concurrent illness or concomitant medication.
Change in the Sum of the Longest Diameter (SLD)
时间窗: Up to 35 Cycles (Each Cycle is 21 Days)
Change in the SLD is assessed by exposure-response modeling
次要结局
- Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax(Up to Cycle 1 (Each Cycle is 21 Days))
- Area Under the Plasma Concentration-Time Curve Over Time from 0 to 24 (AUC0-24) of Venetoclax in Plasma(Up to Cycle 1 (Each Cycle is 21 Days))
- Objective Response Rate (ORR)(Up to 35 Cycles (Each Cycle is 21 Days))
- Maximum Plasma Concentration (Cmax) of Venetoclax(Up to Cycle 1 (Each Cycle is 21 Days))