A Phase 1b/2, Open-label, Randomized Study of Vudalimab in Combination With Chemotherapy or Pembrolizumab in Combination With Chemotherapy as First-line Treatment in Patients With Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Xencor, Inc.
- 入组人数
- 28
- 试验地点
- 17
- 主要终点
- Part 1: Recommended Phase 2 dose of vudalimab in combination with chemotherapy
研究概览
简要总结
The purpose of this study is to identify the recommended dose of vudalimab to be used in combination with chemotherapy (Part 1) and to evaluate the efficacy and safety of vudalimab plus standard of care chemotherapy relative to pembrolizumab plus chemotherapy (Part 2) as first-line treatment in patients with nonsquamous non-small cell lung cancer (NSCLC).
详细描述
This is a Phase 1b/2 study, multicenter, open-label, randomized study in patients with nonsquamous non-small cell lung cancer without prior treatment for metastatic disease. Part 1 is designed to identify the recommended Phase 2 dose (RP2D) of vudalimab, an anti-PD-1/CTLA-4 bispecific antibody, in combination with standard of care (SOC) chemotherapy. Part 2 will evaluate the efficacy and safety vudalimab, at the RP2D, plus SOC relative to pembrolizumab (anti-PD-1) plus SOC chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 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 confirmed, locally advanced (unresectable) or metastatic nonsquamous NSCLC
- •Documented absence of tumor activating EGFR mutation, ALK gene and ROS1 rearrangements, and alterations in any actionable driver oncogenes for which there are locally approved targeted first-line therapies
- •PD-L1 IHC testing documenting TPS < 49%
- •No prior systemic treatment for advanced/metastatic NSCLC.
- •Measurable disease by RECIST 1.1
- •ECOG performance status score of 0 or 1
- •Life expectancy ≥ 3 months
- •Adequate liver, kidney, thyroid and bone marrow function
排除标准
- •Have known active central nervous system metastases and/or carcinomatous meningitis. Patients with treated brain metastases may participate, provided they are radiologically stable
- •Active known or suspected autoimmune disease
- •Has any condition requiring systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medications within 14 days prior to first dose of study drug
- •Interstitial lung disease that is symptomatic
- •Known human immunodeficiency virus (HIV) positive with CD4+ T-cell (CD4+) count < 350 cells/μL, or an HIV viral load greater than 400 copies/mL, or a history of an acquired immunodeficiency syndrome-defining opportunistic infection within the past 12 months, or not on established antiretroviral therapy (ART) for at least 4 weeks prior to initiation of study drug dosing. (HIV positive subjects who do not meet these exclusion criteria are eligible)
- •Positive test for hepatitis C RNA (a patient who is hepatitis C virus [HCV] antibody positive but HCV RNA negative due to documented, curative prior antiviral treatment or natural resolution is eligible)
- •Positive test for hepatitis B surface antigen or hepatitis B core antibody (hBcAb) (a patient whose hBsAg is negative and hBcAb is positive may be enrolled if a hepatitis B virus (HBV) DNA test is negative and the subject is retested for HbsAg and HBV DNA every 2 months)
- •History or evidence of any clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic, or psychiatric) other than NSCLC, that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study evaluations, procedures, or completion
- •Other protocol defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Vudalimab + Carboplatin + Pemetrexed
干预措施: Vudalimab + Carboplatin + Pemetrexed (Combination Product)
Pembrolizumab + Carboplatin + Pemetrexed
干预措施: Pembrolizumab + Carboplatin + Pemetrexed (Combination Product)
结局指标
主要结局
Part 1: Recommended Phase 2 dose of vudalimab in combination with chemotherapy
时间窗: Day 1 to Day 21
Incidence of treatment-emergent adverse events and treatment-related adverse events leading to discontinuation of treatment
Part 2: Progression free survival
时间窗: Day 1 to 2.5 years
Progressive disease per RECIST 1.1 or death, whichever comes first
次要结局
- Changes in circulating tumor DNA (ctDNA)(Day 1 to 1.4 years)
- Trough Serum Drug Concentration (Ctrough)(Day 1 to 1.4 years)
- Area Under the Concentration-time Curve (AUC)(Day 1 to 1.4 years)
- Antitumor activity(Day 1 to 1.4 years)
- Maximum Serum Drug Concentration (Cmax)(Day 1 to 1.4 years)
- Overall survival(Day 1 to 2.5 years)
- Incidence of treatment-emergent adverse events(Time Frame: Day 1 to 1.4 years])