A Study of LOXO-783 Administered as Monotherapy and in Combination With Anticancer Therapies for Patients With Advanced Breast Cancer and Other Solid Tumors With a PIK3CA H1047R Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 260
- 试验地点
- 101
- 主要终点
- Phase 1 a: To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of LOXO-783: Number of patients with dose-limiting toxicities (DLTs)
研究概览
简要总结
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-783. LOXO-783 may be used to treat breast cancer and other solid tumors that have a change in a particular gene (known as the PIK3CA gene). Participation could last up to 36 months (3 years) and possibly longer if the disease does not get worse.
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 advanced breast cancer or another solid tumor with the presence of a phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) H1047R mutation (or other Sponsor and safety review committee (SRC)-approved, activating PIK3CA mutations other than H1047R mutation)
- •Have adequate archival tumor tissue sample available or be approved by the Sponsor for enrollment if no tumor sample is available.
- •Have stopped all cancer treatment and have recovered from the major side effects
- •Have adequate organ function, as measured by blood tests
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Patients must have
- •Measurable disease
- •--- Patients with non-breast tumor types must have at least 1 measurable lesion
- •Non-measurable bone disease (at least 1 bone lesion in breast cancer patients only)
- •For patients with an estrogen receptor (ER)+ breast cancer diagnosis:
- •If female, must be postmenopausal
- •If male, must agree to use hormone suppression
- •Phase 1a:
- •-- Dose escalation and backfill patients:
- •Advanced solid tumor
- •Patients may have had up to 5 prior regimens for advanced disease
- •Phase 1b:
- •ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer
- •Patients may have had up to 5 prior regimens for advanced disease ---- Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
- •ER+/HER2- advanced breast cancer
- •Patients may have had up to 2 prior regimens for advanced disease.
- •ER+/HER2- advanced breast cancer
- •Patients may have had up to 5 prior regimens for advanced disease.
- •---- Prior CDK4/6 inhibitor therapy required.
- •Have a diagnosis of diabetes mellitus Type 2
- •Advanced breast cancer
- •Patients may have had up to 5 prior regimens for advanced disease.
- •Advanced solid tumor
- •Patients may have had up to 3 prior regimens for advanced disease advanced disease
- •ER+/HER2- advanced breast cancer
- •Patients may have had up to 5 prior regimens for advanced disease
- •Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
排除标准
- •Medical Conditions
- •Colorectal cancer
- •Endometrial cancers with specific concurrent oncogenic alterations
- •A history of known active or suspected
- •Diabetes mellitus Type 1 or
- •Diabetes mellitus Type 2 requiring antidiabetic medication (Phase 1a and all parts of Phase 1b except Part C).
- •Serious concomitant systemic disorder
- •Known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement.
- •Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or other clinically significant active disease process
- •Prior exposure to phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) inhibitor(s), except in certain circumstances
研究组 & 干预措施
Phase 1B: Part B
LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
干预措施: Fulvestrant (Drug)
Phase 1B: Part B
LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
干预措施: Abemaciclib (Drug)
Phase 1B: Part B
LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
干预措施: Imlunestrant (Drug)
Phase 1B: Part E
LOXO-783 orally
干预措施: LOXO-783 (Drug)
Phase 1B: Part D
LOXO-783 orally in combination with paclitaxel intravenously
干预措施: Paclitaxel (Drug)
Phase 1B: Part C
LOXO-783 orally in combination with fulvestrant intramuscularly
干预措施: Fulvestrant (Drug)
Phase 1B: Part A
LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally
干预措施: Fulvestrant (Drug)
Phase 1B: Part A
LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally
干预措施: Imlunestrant (Drug)
Phase 1B: Part B
LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
干预措施: LOXO-783 (Drug)
Phase 1B: Part A
LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally
干预措施: Anastrozole, Exemestane, or Letrozole (Drug)
Phase 1B: Part C
LOXO-783 orally in combination with fulvestrant intramuscularly
干预措施: LOXO-783 (Drug)
Phase 1B: Part B
LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
干预措施: Anastrozole, Exemestane, or Letrozole (Drug)
Phase 1A: LOXO-783 Monotherapy Dose Escalation
LOXO-783 administered orally
干预措施: LOXO-783 (Drug)
Phase 1B: Part F
Multiple randomized dose levels of LOXO-783 orally with fulvestrant intramuscularly
干预措施: LOXO-783 (Drug)
Phase 1B: Part F
Multiple randomized dose levels of LOXO-783 orally with fulvestrant intramuscularly
干预措施: Fulvestrant (Drug)
Phase 1B: Part A
LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally
干预措施: LOXO-783 (Drug)
Phase 1B: Part D
LOXO-783 orally in combination with paclitaxel intravenously
干预措施: LOXO-783 (Drug)
结局指标
主要结局
Phase 1 a: To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of LOXO-783: Number of patients with dose-limiting toxicities (DLTs)
时间窗: During the first 28-day cycle of LOXO-783 treatment
Number of patients with DLTs
Phase 1 a: To determine the MTD/RP2D of LOXO-783: Number of patients with DLT-equivalent toxicities
时间窗: During the first 28-day cycle of LOXO-783 treatment
Number of patients with DLT-equivalent toxicities
次要结局
- To assess the PK of LOXO-783: Maximum drug concentration (Cmax)(Up to 2 months)
- To evaluate the preliminary antitumor activity of LOXO-783: Time to response (TTR)(Up to approximately 36 months or 3 years)
- To evaluate the preliminary antitumor activity of LOXO-783: Progression free survival (PFS)(Up to approximately 36 months or 3 years)
- To assess the pharmacokinetics (PK) of LOXO-783: Area under the concentration versus time curve (AUC)(Up to 2 months)
- To evaluate the preliminary antitumor activity of LOXO-783: Duration of response (DOR)(Up to approximately 36 months or 3 years)
- To evaluate the preliminary antitumor activity of LOXO-783: Disease control rate (DCR)(Up to approximately 36 months or 3 years)
- To evaluate the preliminary antitumor activity of LOXO-783: Overall survival (OS)(Up to approximately 36 months or 3 years)
- To evaluate the preliminary antitumor activity of LOXO-783: Overall response rate (ORR)(Up to approximately 36 months or 3 years)
- To evaluate the preliminary antitumor activity of LOXO-783: Best overall response (BOR)(Up to approximately 36 months or 3 years)
- To evaluate the preliminary antitumor activity of LOXO-783: Clinical benefit rate (CBR)(Up to approximately 36 months or 3 years)