A Phase 1a/1b Study of CXCR4 Peptide Antagonist (LY2510924) Administered in Combination With the Anti-PD-L1 Antibody, Durvalumab (MEDI4736), in Advanced Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 主要终点
- Maximum Tolerated Dose (MTD) of LY2510924
研究概览
简要总结
The main purpose of this study is to evaluate the safety and tolerability of chemokine (C-X-C Motif) receptor 4 (CXCR4) peptide antagonist LY2510924 and durvalumab for phase 1a and 1b in participants with advanced refractory solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Phase 1a: Have histologic or cytologic confirmation of advanced solid tumor
- •Have at least 1 measurable lesion assessable using standard techniques by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
- •Have adequate organ function
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Have provided tissue from a newly obtained core or excisional biopsy of a tumor lesion or a recent biopsy defined by ≤3 years since last documented progression of disease
- •Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator
排除标准
- •Have a serious concomitant systemic disorder including human immunodeficiency virus (HIV), active hepatitis B virus (HBV), active HCV, active autoimmune disorder or disease requiring high dose of steroids
- •Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection or chronic diarrhea
- •Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis
- •Have an active infection requiring systemic therapy
- •Have had prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-L1, anti-PD-L2, or anticytotoxic T lymphocyte-associated antigen-4 antibody
- •Moderate or severe cardiovascular disease
- •Have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment
- •Have received a live vaccine within 30 days before the first dose of study treatment
研究组 & 干预措施
20 mg LY2510924 + 1500 mg Durvalumab
20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).
干预措施: LY2510924 (Drug)
20 mg LY2510924 + 1500 mg Durvalumab
20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).
干预措施: Durvalumab (Drug)
30 mg LY2510924 + 1500 mg Durvalumab
30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
干预措施: LY2510924 (Drug)
30 mg LY2510924 + 1500 mg Durvalumab
30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
干预措施: Durvalumab (Drug)
40 mg LY2510924 + 1500 mg Durvalumab
40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
干预措施: LY2510924 (Drug)
40 mg LY2510924 + 1500 mg Durvalumab
40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
干预措施: Durvalumab (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of LY2510924
时间窗: Cycle 1 (28 Days)
MTD was determined after the evaluation of Phase 1a portion of the trial. For Phase 1a, any DLT-equivalent toxicities observed in Cycle 2 and beyond were also be considered in dose escalation and determining MTD/recommended Phase 2 dose. See outcome measure number 1 for the DLT criterion.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
时间窗: Cycle 1 (28 Days)
DLT is defined as 1 of the following adverse events(AE) reported during the Phase 1a DLT observation period,if considered to be definitely,probably,or possibly related to either study regimen by the investigator;and fulfills any 1 of the following criterion using(NCI)CTCAE version(v)4.03:Grade4 immune-related AE,Grade4 non-laboratory AE,any CTCAE Grade ≥3 QT prolongation AE,≥Grade3 colitis or noninfectious pneumonitis irrespective of duration,Grade3 immune-related AE(excluding colitis,QT prolongation,or pneumonitis) that does not downgrade to Grade2 within 3 days after onset of event despite optimal medical management including systemic corticosteroids,or does not downgrade to ≤Grade 1 or baseline within 14 days,Grade2 pneumonitis that does not resolve to ≤Grade 1 within 3 days of the initiation of maximal supportive care,including corticosteroid therapy,Grade3 toxicity lasting an extended time despite optimal supportive care and there were also laboratory abnormalities criterion.
次要结局
- Pharmacokinetics: Area Under the Concentration-Time Curve (AUC [0-∞]) of LY2510924 When Co-Administered With Durvalumab(Cycle 1 Day 1: Predose, 0.5, 2, 4, 6, 8, 24-30 hours; Day 15: Predose, 0.5, 2, 4, 6, 8 hours)
- Number of Participants With Anti-Durvalumab Antibodies When Administered in Combination With LY2510924(Predose Cycle 1 Day 1 through 90 Day Post Treatment Follow Up (Up To 12 Months))
- Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)](Baseline through Measured Progressive Disease or Death (Up To 12 Months))
- Percentage of Participants With CR, PR, or Stable Disease (SD) (Disease Control Rate [DCR])(Baseline through Measured Progressive Disease (Up To 12 Months))