A Randomized, Double-blind, Placebo-controlled, Phase 2 Study Evaluating Efficacy and Safety of Inupadenant in Combination With Carboplatin and Pemetrexed in Adults With Nonsquamous Non-small Cell Lung Cancer Who Have Progressed on Immunotherapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 36
- 试验地点
- 21
- 主要终点
- Dose-finding to determine recommended Phase 2 dose
研究概览
简要总结
The study will first determine the optimal dose of inupadenant to be given in combination with carboplatin and pemetrexed to patients that progressed after receiving first line anti-PD(L)1 treatment for locally advanced or metastatic non-small cell lung cancer. The efficacy and safety of the combination is then compared to standard of care carboplatin and pemetrexed in the same populations.
详细描述
The study is composed of two parts. Part 1 follows an open-label, dose-finding design where individual cohorts are treated with various dose levels of inupadenant combined with standard of care dosing of carboplatin and pemetrexed. The recommended phase 2 dose is determined prior to initiation of Part 2 which then compares inupadenant to placebo with both arms treated in combination with standard of care carboplatin and pemetrexed.
Participants in both parts are enrolled from two populations of patients with nonsquamous NSCLC that have progressed after first line treatment as follows: non-resectable patients treated with chemoradiotherapy followed by anti-PD-(L)1 or metastatic patients treated with anti-PD-(L)1 therapy without chemotherapy.
Imaging, safety and PRO assessments are performed during the treatment and follow-up phase as well as pharmacokinetic and other exploratory analyses.
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)
盲法说明
Quadruple masking : The dose-finding part (Part 1) of this study is open-label whereas the randomized part (Part 2) is double-blinded. Therefore, for Part 2, the subject, the Investigator and Sponsor personnel or delegate(s) who are involved in the treatment administration or clinical evaluation of the subjects will be unaware of the group assignments. The chemotherapy agents administered during Part 2 will be open label.
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
- •Confirmed diagnosis of metastatic (Stage IV) or locally advanced, unresectable (Stage III) NSCLC of nonsquamous pathology
- •Measurable disease as defined by RECIST v1.1
- •PD-L1 expression status available at or after the time of diagnosis. All levels of expression are eligible.
- •Existing biopsy taken within 4 years prior to entering trial or provide fresh biopsy where safe and feasible
- •At least 12 weeks of treatment with only 1 anti-PD-(L)1 agent (mono or with IO combo) in the metastatic setting, OR at least 12 weeks of anti-PD-(L)1 agent (mono or with IO combo) following CRT in the unresectable, Stage III setting
- •ECOG performance status of 0 to 1.
排除标准
- •Symptomatic central nervous system (CNS) metastases or leptomeningeal disease.
- •EGFR, ALK, or ROS1 mutation.
- •Autoimmune disease requiring systemic treatment or immunodeficiency requiring concurrent use of systemic immunosuppressants or corticosteroids
- •Hepatitis B or C infection unless adequately treated with no detectable viral load; Human immunodeficiency virus (HIV) unless well-controlled disease on therapy.
- •History of life-threatening toxicity related to prior immune therapy
- •Uncontrolled or significant cardiovascular disease
- •Pregnant or breast-feeding
- •Lack of agreement to use highly effective method of contraception during treatment and for 6 months after the last administration of chemotherapy
研究组 & 干预措施
Part 2, active treatment
Treatment with inupadenant combined with carboplatin and pemetrexed
干预措施: Pemetrexed (Drug)
Part 1, open label
Inupadenant will be given at one or more dose levels to determine the recommended Phase 2 dose (RP2D).
干预措施: inupadenant (Drug)
Part 1, open label
Inupadenant will be given at one or more dose levels to determine the recommended Phase 2 dose (RP2D).
干预措施: Carboplatin (Drug)
Part 1, open label
Inupadenant will be given at one or more dose levels to determine the recommended Phase 2 dose (RP2D).
干预措施: Pemetrexed (Drug)
Part 2, active treatment
Treatment with inupadenant combined with carboplatin and pemetrexed
干预措施: inupadenant (Drug)
Part 2, active treatment
Treatment with inupadenant combined with carboplatin and pemetrexed
干预措施: Carboplatin (Drug)
Part 2, placebo
Treatment with matched placebo combined with carboplatin and pemetrexed
干预措施: Placebo (Drug)
Part 2, placebo
Treatment with matched placebo combined with carboplatin and pemetrexed
干预措施: Carboplatin (Drug)
Part 2, placebo
Treatment with matched placebo combined with carboplatin and pemetrexed
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Dose-finding to determine recommended Phase 2 dose
时间窗: At the end of Cycle 1 (each cycle is 21 days)
Incidence of dose-limiting toxicities
Incidence of treatment-emergent adverse events [Safety and Tolerability]
时间窗: Duration of intervention (up to 24 months) plus 30 days follow-up or up to database lock
Incidence of adverse events (AEs), serious adverse events, AEs leading to discontinuation, deaths, and clinically significant laboratory abnormalities.
Progression-free survival [Efficacy]
时间窗: From randomization to first-documented radiological progression or date of death from any cause, whichever comes first, assessed up to 24 months.
Time from first dose to the date of first documented radiologic progression per RECIST v1.1 or time of death, whichever comes first
次要结局
- Overall Response Rate [Efficacy](From randomization to first-documented radiological improvement, if applicable, assessed up to 24 months or up to database lock.)
- Duration of Response [Efficacy](From first-documented CR or PR to first radiological progression or date of death, whichever comes first, assessed up to 24 months or up to database lock.)
- Percent Change in Tumor Size [Efficacy](From randomization to the documented radiological assessment with the smallest tumor size sum, assessed up to 24 months or up to database lock.)
- Disease Control Rate [Efficacy](From randomization to second-documented radiological CR, PR or SD, if applicable, assessed up to 24 months or up to database lock.)
- Overall Survival [Efficacy](From randomization to death due to any cause, assessed up to 24 months or up to database lock.)