A Phase 1 Multicenter Global First in Human Study of the CD73 Inhibitor LY3475070 as Monotherapy or in Combination With Pembrolizumab in Patients With Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 12
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The reason for this study is to see if the CD73 inhibitor LY3475070 alone or in combination with pembrolizumab is safe and effective in participants with advanced cancer.
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
- 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
- •Participants must have certain types of cancer such as breast cancer, pancreatic cancer, lung cancer, kidney cancer, skin cancer (melanoma), prostate cancer, and ovarian cancer
- •Participants must have stopped other forms of treatment for the cancer
- •In the expansion cohorts participants must be able and willing to provide a sample of the tumor before beginning treatment and a sample during the treatment. For certain tumor types, the result of a test on the tumor sample may exclude the participant from the study
- •Participants must not be pregnant, and must agree to use birth control
- •Participants must have progressed through or be intolerant to therapies with known clinical benefit
排除标准
- •Participants must not have a current untreated tuberculosis, lung disease, heart disease, uncontrolled HIV, autoimmune disease, active hepatitis B or C virus infection or using corticosteroids
- •Participant must not have cancer that has spread to the brain
- •Participant must not have received a vaccine within the last 30 days
- •Participant must not have had bowel obstruction within the last 6 months, or intestinal surgery
- •Participant must not have an infection that is currently being treated
研究组 & 干预措施
Phase 1b Cohort C1 LY3475070 + Pembrolizumab (dose expansion)
LY3475070 administered orally and pembrolizumab administered IV.
Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
干预措施: LY3475070 (Drug)
Phase 1a Cohort A LY3475070 (dose escalation)
Participants received 150 milligram (mg) once daily or 300 mg once daily or 300mg twice daily or 600mg once daily oral LY3475070 on a 21-day cycle until progressive disease, unacceptable toxicity or other criterion for study discontinuation is met.
干预措施: LY3475070 (Drug)
Phase 1a Cohort B LY3475070 + Pembrolizumab (dose escalation)
Participants received 150 mg once daily or 150 mg twice daily or 300 mg once daily or 300mg twice daily oral LY3475070 on a 21-day cycle in combination with an intravenous infusion of 200mg pembrolizumab on day 1 until progressive disease, unacceptable toxicity or other criterion for study discontinuation is met.
干预措施: LY3475070 (Drug)
Phase 1a Cohort B LY3475070 + Pembrolizumab (dose escalation)
Participants received 150 mg once daily or 150 mg twice daily or 300 mg once daily or 300mg twice daily oral LY3475070 on a 21-day cycle in combination with an intravenous infusion of 200mg pembrolizumab on day 1 until progressive disease, unacceptable toxicity or other criterion for study discontinuation is met.
干预措施: Pembrolizumab (Drug)
Phase 1b Cohort C1 LY3475070 + Pembrolizumab (dose expansion)
LY3475070 administered orally and pembrolizumab administered IV.
Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
干预措施: Pembrolizumab (Drug)
Phase 1b Cohort C2 LY3475070 (dose expansion)
LY3475070 administered orally.
Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
干预措施: LY3475070 (Drug)
Phase 1b Cohort D1 LY3475070 + Pembrolizumab (dose expansion)
LY3475070 administered orally and pembrolizumab administered IV.
Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
干预措施: LY3475070 (Drug)
Phase 1b Cohort D1 LY3475070 + Pembrolizumab (dose expansion)
LY3475070 administered orally and pembrolizumab administered IV.
Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
干预措施: Pembrolizumab (Drug)
Phase 1b Cohort D2 LY3475070 (dose expansion)
LY3475070 administered orally.
Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
干预措施: LY3475070 (Drug)
Phase 1b Cohort E LY3475070 + Pembrolizumab (dose expansion)
LY3475070 administered orally and pembrolizumab administered IV.
Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
干预措施: LY3475070 (Drug)
Phase 1b Cohort E LY3475070 + Pembrolizumab (dose expansion)
LY3475070 administered orally and pembrolizumab administered IV.
Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
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 from the first dose
A DLT is defined as an adverse event that is likely related to the study medication or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events) version 5.0: * Grade 3 thrombocytopenia associated with clinically significant bleeding and requiring platelet transfusion or Grade 4 thrombocytopenia of any duration. * Grade ≥3 febrile neutropenia * Grade ≥3 anemia requiring a blood transfusion * Other Grade ≥4 toxicities, excluding few nonhematologic Toxicities * Any other significant toxicity deemed by the investigatory to be dose-limiting, such as: any toxicity that is possibly related to the study medication that requires the withdrawal of the participant from the study during 28-day DLT observation period), persistent Grade \>2 toxicities causing a delay of LY3475070 study treatment \>14 days during the 28-day DLT observation period.
次要结局
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Eight Hours (AUC[0-8]) of LY3475070(Cycle 1 Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose))
- PK: Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCtau) of LY3475070(Cycle 2 Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose for the QD arms, Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose for the BID arms))
- PK: Maximum Concentration (Cmax) of LY3475070(Day 1 of Cycles 1 and 2 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose for the QD arms; Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose for the BID arms))
- Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR)(Baseline through Disease Progression or Death (Estimated at up to 10.4 Months))
- Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease (SD)(Baseline through Measured Progressive Disease (Estimated at up to 10.4 Months))
- Progression-Free Survival (PFS)(Baseline to Objective Progression or Death Due to Any Cause (Estimated at up to 10.4 Months))