A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of AK-01 as Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 3
- 主要终点
- Phase 1: Maximum Tolerated Dose
研究概览
简要总结
This two-part study consists of a phase 1 dose escalation study in participants with locally advanced or metastatic solid tumors, and a phase 2 portion in up to 3 groups with either small cell lung cancer, breast cancer and/or one other solid tumor type.
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
盲法说明
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
- •Have received at least 1 but no more than 4 prior systemic therapies
- •Have adequate organ function
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Have estimated life expectancy greater than or equal to (≥)12 weeks
- •Have fully recovered from radiation therapy or surgery, and are recovering from any acute adverse effects of other cancer therapies
- •Have discontinued all chemotherapy, investigational therapy, molecularly-targeted therapy, and cancer-related hormonal therapy at least 14 days prior, biologic or immunotherapeutic therapy at least 21 days prior, or mitomycin-C or nitrosoureas at least 6 weeks prior
- •Female participants with reproductive potential agree to use 2 forms of highly effective contraception during the study and for the following 3 months
- •Male participants must use a barrier method of contraception during the study and for the following 3 months
- •Have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor)
- •Have disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1
- •Have evidence of a solid tumor that is locally advanced and/or metastatic, and in:
- •Small Cell Lung Cancer (SCLC), must have failed platinum-containing therapy
- •Breast Cancer, be Estrogen Receptor positive and/or Progesterone Receptor positive, but Human Epidermal Growth Factor Receptor 2 (HER2) negative, and must have failed a hormone therapy and a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor
- •Triple negative breast cancer (TNBC) and failed standard therapy
- •Squamous cell cancers of the head neck associated with the human papilloma virus (HPV), and have failed standard therapy
- •Other solid tumor type that has been approved by the sponsor
排除标准
- •Have symptomatic central nervous system (CNS) metastasis (unless asymptomatic and not current receiving corticosteroids) or a primary tumor of the CNS
- •Have a medical condition that precludes participation (swallowing disorder, organ transplant, pregnant or nursing, HIV, active Hepatitis B or C, cardiac disease, history of major surgery in upper gastrointestinal (GI) tract or GI disease, hypokalemia, hypomagnesaemia or hypocalcaemia that cannot be controlled)
研究组 & 干预措施
25 milligrams (mg) LY3295668 (Phase 1)
25 milligrams (mg) LY3295668 twice daily (BID) administered orally in 21-day cycles.
干预措施: LY3295668 (Drug)
50 mg LY3295668 (Phase 1)
50 mg LY3295668 BID administered orally in 21-day cycles.
干预措施: LY3295668 (Drug)
75 mg LY3295668 (Phase 1)
75 mg LY3295668 BID administered orally in 21-day cycles.
干预措施: LY3295668 (Drug)
25 mg LY3295668 (Phase 2)
25 mg LY3295668 BID administered orally in 21-day cycles.
干预措施: LY3295668 (Drug)
结局指标
主要结局
Phase 1: Maximum Tolerated Dose
时间窗: Cycle 1 (21 days)
Maximum Tolerated Dose (MTD) was defined as the dose immediately below the dose at which ≥2/3, ≥2/6, or ≥3/9 participants in a cohort experienced a dose limiting toxicity (DLT) during the first 21 days of treatment (Cycle 1) in Phase 1.
Phase 2: Percentage of Participants Who Achieved Partial Response (PR) or Complete Response (CR) [Objective Response Rate (ORR)]
时间窗: Baseline to Objective Disease Progression (Up to 11 months)
Objective response rate (ORR) was defined as a percentage of responders who achieved complete response or partial response (CR+PR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Complete response (CR) is defined as disappearance of all target (and non-target) lesions, and no appearance of new lesion. Partial response (PR) was defined as at least a 30% decrease in the sum of longest diameters (LD) of target lesions, taking as reference the baseline sum of LD, no progression of non-target lesions, and no appearance of new lesions.
次要结局
- Phase 2: Pharmacokinetic (PK): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC[0-12]) (Phase 2)(Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 - 12 hours postdose; Cycle 1: Day 2 and Day 8 predose)
- Phase 2: PK: Apparent Terminal Elimination Half-life (t1/2)(Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8-12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose)
- Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Neutrophils (Segmented and Blended)(Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months))
- Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Lymphocytes(Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months))
- Phase 2: PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-dose (AUC[0-24])(Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8-12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose)
- Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events(Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months))
- Phase 2: PK: Apparent Total Plasma Clearance (CL/F)(Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 -12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose)
- Phase 2: PK: Apparent Volume of Distribution (Vz/F)(Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 -12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose)
- Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 White Blood Cell Count (WBC)(Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months))
- Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events(Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months))
- Phase 2: PK: Maximum Observed Plasma Concentration (Cmax)(Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose)
- Phase 2: PK: Time of Maximum Observed Plasma Concentration (Tmax)(Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose)