A Phase Ib /II Trial of Pembrolizumab and Idelalisib in Patients With Non-small Cell Lung Cancer (NSCLC) Who Have Failed Immune Checkpoint Inhibitor
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03
研究概览
简要总结
This is a phase 1b/2 study to determine the safety and effectiveness of the combination of pembrolizumab and idelalisib in NSCLC patients whose disease has stopped responding to immune therapy. This study is being done to see if adding another immune modulator (idelalisib) to standard pembrolizumab will increase response rates, compared to the response seen with pembrolizumab alone.
详细描述
This is a phase 1b/2 study to determine the safety and effectiveness of the combination of pembrolizumab and idelalisib in NSCLC patients whose disease has stopped responding to immune therapy. Pembrolizumab is an anti-PD-1 immunotherapy that is given intravenously and is approved for treatment of malignant NSCLC. Idelalisib is the first-in-class oral PI3K-δ inhibitor that is approved for treatment of certain forms of leukemia and lymphoma.
Immune checkpoint inhibitors (such as anti-PD-1) are effective in treating NSCLC as a single agent, but overall response isn't optimal; overall response rates (ORR) are only ~20% on average. The goal of this study is to see whether combining standard therapy with additional immune modulators will increase response rates, compared to the response seen with pembrolizumab monotherapy.
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
- •Have at least one measurable lesion
- •Have an ECOG Performance Status of 1 or less
- •Demonstrate adequate organ function as defined in the protocol.
- •Female subjects of childbearing potential must have a negative pregnancy test before starting treatment; they must also be willing to use two methods of birth control or abstain from heterosexual activity for the duration of the study.
- •Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through the duration of the study.
排除标准
- •Is currently receiving study drug in another trial; or has participated in an investigational drug study within 3 weeks of the first dose of treatment.
- •Is within 3 weeks of most recent chemotherapy.
- •Has a history of hypersensitivity to pembrolizumab or idelalisib, or any of their excipients.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated, stable, brain metastases may participate; carcinomatous meningitis is excluded regardless of clinical stability.
- •Has known history of non-infectious pneumonitis that required steroid use or has current pneumonitis.
- •Has a known history of active TB (Bacillus Tuberculosis)
- •Has active autoimmune disease that has required treatment; known history of Human Immunodeficiency Virus (HIV); known active Hepatitis B or Hepatitis C.
- •Has an active infection requiring systemic therapy.
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
研究组 & 干预措施
Phase 1 Dose Escalation
Sequential cohorts of 3 patients will receive pembrolizumab 200 mg intravenously every 3 weeks, in addition to the oral drug, idelalisib, every day for 21 days. The first group of 3 will receive idelalisib 50 mg twice daily; the next cohort will receive idelalisib 100 mg twice daily; the last cohort will receive idelalisib 150 mg twice daily.
干预措施: Pembrolizumab (Drug)
Phase 1 Dose Escalation
Sequential cohorts of 3 patients will receive pembrolizumab 200 mg intravenously every 3 weeks, in addition to the oral drug, idelalisib, every day for 21 days. The first group of 3 will receive idelalisib 50 mg twice daily; the next cohort will receive idelalisib 100 mg twice daily; the last cohort will receive idelalisib 150 mg twice daily.
干预措施: Idelalisib (Drug)
Phase 2 Efficacy
All patients in the efficacy assessment phase will be treated with pembrolizumab (200 mg intravenously every 3 weeks) in combination with oral idelalisib (dose not exceeding 150 mg twice daily, per the phase 1 assessment) for 18 weeks before maintenance with pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years, until disease progression or unacceptable toxicity.
干预措施: Pembrolizumab (Drug)
Phase 2 Efficacy
All patients in the efficacy assessment phase will be treated with pembrolizumab (200 mg intravenously every 3 weeks) in combination with oral idelalisib (dose not exceeding 150 mg twice daily, per the phase 1 assessment) for 18 weeks before maintenance with pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years, until disease progression or unacceptable toxicity.
干预措施: Idelalisib (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicity (DLT) Events as Assessed by CTCAE v4.03
时间窗: First 9 weeks at each dose level
Modified 3+3 dose escalation design will be used to determine whether the addition of idelalisib to standard pembrolizumab is safe and tolerable in checkpoint inhibitor refractory NSCLC patients. An initial cohort of 3 patients will receive 50 mg twice daily idelalisib with standard pembrolizumab. If none of the 3 patients develop a DLT, another 3 patients will be enrolled. Dose will be escalated or de-escalated based on the occurrence of DLTs. All events will be assessed for possible, probable, or definite relation to idelalisib.
次要结局
- Dose-Finding Assessment for Optimum Dose of Idelalisib in Combination With Pembrolizumab(18-27 weeks)
- Overall Response Rates (ORR) to Combination Therapy(18 weeks - 2 years)
研究者
Asha Nayak
Professor of Medicine
Augusta University