A Phase 1a/1b Study of LY3405105 Administered to Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 54
- 试验地点
- 17
- 主要终点
- Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The main purpose of this study is to investigate the safety of LY3405105 in participants with advanced cancer. The study has two parts phase 1a and phase 1b. Participants will only enroll in one part.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Have histological or cytological evidence of a diagnosis of a solid tumor cancer that is advanced and/or metastatic
- •Have available archived tissue for exploratory biomarker analysis
- •Have adequate organ function
- •Have discontinued all previous treatments for cancer and recovered from their side effects
- •Are able to swallow capsules/tablets
- •Cohort 1: Triple-negative breast cancer (TNBC).
- •Cohort 2: Clear cell ovarian cancer, endometrioid ovarian cancer, or endometrioid endometrial carcinoma with a LOF mutation in one or more of the following genes: ARID1A, KMT2C (MLL3), KMT2D (MLL2), or KDM6A (UTX).
- •Cohort 3: Soft tissue sarcoma or sarcomatoid/rhabdoid malignancy with loss of expression of INI1, BRG1, or BRM by immunohistochemistry or a LOF mutation in one or more of the following genes: ARID1A, SMARCA2, SMARCA4, or SMARCB
- •Participants aged ≥ 12 years with a body weight of ≥ 40 kilogram (kg) are acceptable for Cohorts
- •Participants with synovial sarcoma and a confirmed SS18-SSX gene fusion are also eligible.
- •Cohort 4: Epithelioid sarcoma with INI1 loss of expression by immunohistochemistry or SMARCB1 LOF mutation. Participants aged ≥ 12 years with a body weight of ≥ 40 kilogram (kg) are acceptable for Cohorts
- •Cohort 5: Bladder cancer with a LOF mutation in one or more of the following genes: ARID1A, KMT2C (MLL3), KMT2D (MLL2), or KDM6A (UTX).
排除标准
- •Have symptomatic central nervous system (CNS) malignancy or metastasis
- •Have symptomatic human immunodeficiency virus (HIV), Hepatitis A, B, or C
- •Have congestive heart failure
- •Are breastfeeding
研究组 & 干预措施
LY3405105
This study was designed to be conducted in two phases:
Phase 1a: This is a dose-escalation phase with a starting dose of LY3405105 1 milligram (mg) once daily (Part A1) or 2 mg three times per week (Part A2) on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Each dose-level will be determined and will have participants enrolled to it based on dose-limiting toxicity rate observed at previous dose-level. Intermediate, alternate, or higher dose levels will be explored if deemed necessary.
Phase 1b: This is a dose-expansion phase designed to explore the anti-tumor activity of recommended LY3405105 dose and dosing schedule determined in phase 1a, in participants with multiple tumor types.
[Phase 1b was planned but not initiated based on the sponsor's decision and limited efficacy observed in phase 1a]
干预措施: LY3405105 (Drug)
结局指标
主要结局
Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (Up To 28 Days)
A DLT is a clinically significant adverse event that is possibly related to the study drug and fulfils any one of the following criteria using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v4.0: 1\) Nonhematologic Grade ≥3 toxicity, except nausea, constipation, diarrhoea, vomiting or electrolyte disturbance lasting for \<72 hours and can be controlled with treatment, fatigue/anorexia lasting for \<5 days, transient grade 3 elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), without evidence of other hepatic injury; 2) Total bilirubin \>2×upper limit of normal (ULN) with ALT/AST \>3×ULN in the absence of cholestasis (alkaline phosphatase \<2×ULN); 3) Grade 4 neutropenia \>5 days duration, Any febrile neutropenia, Grade 4 thrombocytopenia of any duration, Grade 3 thrombocytopenia with clinically significant bleeding, Grade 3/4 anemia or any other significant toxicity deemed to be dose limiting by investigators.
Phase 1b: Objective Response Rate (ORR): Percentage of Participants With a Confirmed Complete Response (CR) or Partial Response (PR)
时间窗: Baseline through Measured Progressive Disease (Estimated up to 6 Months)
ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.
次要结局
- Phase 1a (Part A1): Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY3405105(Cycle 1 Day 1 (Predose, 1, 2, 4, 6, 8, 24 hours post-dose))
- Phase 1a (Part A1): PK: Area Under the Concentration Versus Time Curve During One Dosing Interval [AUC(Tau)] of LY3405105(Cycle 1 Day 15 (Predose, 1, 2, 4, 6, 8, 24 hours post-dose))
- Phase 1a (Part A2): PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3405105(Cycle 1 Day 1 (Predose, 1, 2, 4, 6, 8, 24, 48 hours post-dose))
- Phase 1a (Part A2): PK: Area Under the Concentration Versus Time Curve During One Dosing Interval [AUC(Tau)] of LY3405105(Cycle 1 Day 15 (Predose, 1, 2, 4, 6, 8, 24, 48 hours post-dose))
- Phase 1a: Objective Response Rate (ORR): Percentage of Participants With a Confirmed Complete Response (CR) or Partial Response (PR)(Baseline through Measured Progressive Disease (Up To 349 Days))
- Phase 1a: Disease Control Rate (DCR): Percentage of Participants Who Exhibit Stable Disease (SD), Confirmed CR or PR(Baseline through Measured Progressive Disease (Up To 349 Days))
- Phase 1a: Duration of Response (DOR)(Date of Confirmed CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 12 Months))
- Phase 1a: Time to Response (TTR)(Baseline to Date of Confirmed CR or PR (Estimated up to 6 Months))
- Phase 1b: Progression Free Survival (PFS)(Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 12 Months))
- Phase 1b: Overall Survival (OS)(Baseline to Date of Death from Any Cause (Estimated up to 12 Months))