An Open Label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of IDE574 as Monotherapy in Locally Advanced or Metastatic Solid Tumors and as Combination Therapy With Fulvestrant in Locally Advanced or Metastatic ER+, HER2- Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 11
- 主要终点
- Safety and Tolerability of IDE574 in Part 1 A Monotherapy Dose escalation
研究概览
简要总结
IDE574 is a synthetically manufactured small molecule inhibitor that co-targets the lysine acetyltransferase enzymes KAT6 and KAT7.
The purpose of this study is to evaluate the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of IDE574 as monotherapy in participants with locally advanced or metastatic solid tumors and as combination therapy with fulvestrant in participants with advanced or metastatic ER+, HER2- breast cancer.
详细描述
Part 1 - Monotherapy Dose Escalation and Expansion:
Part 1A - Monotherapy Dose Escalation Part 1A will evaluate increasing doses of IDE574 to assess safety, tolerability and to determine dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) or the recommended dose for expansion (RDE) in subjects with advanced or metastatic ER+, HER2- breast cancer, non-small cell lung cancer, castration-resistant prostate cancer and microsatellite-stable colorectal cancer.
Part 1B - Monotherapy Dose Expansion Part 1B will evaluate in ER+ HER2- advanced or metastatic breast cancer at the potential dose level(s) determined to be safe and tolerable during monotherapy dose escalation Part 1A. In parallel, a basket cohort may be enrolled at or below the highest safe dose level(s) determined to be safe and tolerable in Part 1A.
Part 2 - Combination Dose Escalation and Expansion
Part 2A - IDE574 Combination Therapy with Fulvestrant Dose Escalation Part 2A will evaluate participants with ER+ HER2- advanced or metastatic breast cancer with escalating doses of IDE574 in combination with fulvestrant to assess safety, tolerability and to determine DLTs, MTD or RDE.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Archival Tissue sample for testing
- •Part 1A - Participants with advanced or metastatic ER+, HER2- breast cancer, NSCLC, CRPC, and MSS colorectal adenocarcinoma who have progressed on/after at least one line of standard of care therapy or are intolerant to additional effective therapies.
- •Parts 1B, 2A and 2B: Participants with ER+, HER2- breast cancer who have progressed after at least 1 prior line of treatment with an endocrine therapy and a CDK4/6 inhibitor
- •Female participants with ER+, HER2- breast cancer considered to be of childbearing potential (or have tubal ligations only) must be willing to undergo medically induced menopause (Parts 2A and B only)
- •Female participants of nonchildbearing potential with ER+, HER2- breast cancer must meet at least 1 of the following criteria: Age ≥ 60 years or age <60 years with absence of menstruation for at least 12 months, or had prior removal of both ovaries
- •Have Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤
- •Have adequate bone marrow, renal and liver function.
- •Life expectancy of >3 months
- •Able to safely administer and retain orally administered study treatment
- •Able to comply with contraceptive/barrier requirements
排除标准
- •Known symptomatic brain metastases or leptomeningeal metastasis
- •Known primary CNS malignancy and any other malignancies within 2 years prior to the first dose with the exception of adequately treated localized tumor.
- •Have impairment of GI function or GI disease that may significantly alter the absorption of IDE
- •Have active liver or biliary disease.
- •Have active, uncontrolled bacterial, fungal, or viral infection
- •Have clinically significant cardiac abnormalities and/or blood clotting events within 6 months before the first dose
- •If participants had adverse reactions to previous experimental antitumor treatment that have not recovered to Grade ≤ 1
- •Prior irradiation to >25% of the bone marrow.
- •Known or suspected hypersensitivity to IDE574/excipients or components (Parts 1 & 2) or fulvestrant/excipients or components (Part 2 only)
研究组 & 干预措施
Combination Dose Escalation (Part 2A) IDE574 + Fulvestrant
Participants with ER+ HER2- advanced or metastatic breast cancer will be treated with escalating doses of IDE574 in combination with fulvestrant
干预措施: IDE574 (Drug)
Monotherapy Dose Escalation (Part 1A)
Participants with the appropriate tumor types will be treated with escalating doses of IDE574
干预措施: IDE574 (Drug)
Monotherapy Dose Expansion (Part 1B)
Participants with ER+ HER2- advanced or metastatic breast cancer will be treated using the chosen monotherapy dose(s) of IDE574
干预措施: IDE574 (Drug)
Combination Dose Escalation (Part 2A) IDE574 + Fulvestrant
Participants with ER+ HER2- advanced or metastatic breast cancer will be treated with escalating doses of IDE574 in combination with fulvestrant
干预措施: Fulvestrant injection (Drug)
Combination Dose Expansion (Part 2B)
Participants with ER+ HER2- advanced or metastatic breast cancer will be treated using the chosen combination dose(s) of IDE574 + Fulvestrant
干预措施: IDE574 (Drug)
Combination Dose Expansion (Part 2B)
Participants with ER+ HER2- advanced or metastatic breast cancer will be treated using the chosen combination dose(s) of IDE574 + Fulvestrant
干预措施: Fulvestrant injection (Drug)
结局指标
主要结局
Safety and Tolerability of IDE574 in Part 1 A Monotherapy Dose escalation
时间窗: 21 days following the first dose of IDE574
incidence of DLT; incidence and severity of AEs/serious adverse events (SAEs) graded based on CTCAE V6.0
Safety and Tolerability of IDE574 in Part 1B Monotherapy Dose expansion based on incidence and severity of AEs/SAEs
时间窗: Approximately 24 months total study duration
Incidence and severity of AEs/SAEs graded based on CTCAE V6.0
To evaluate anti-tumor activity of IDE574 of IDE574 in Part 1B Monotherapy Dose expansion based on the ORR per RECIST version 1.1
时间窗: Approximately 24 months total study duration
Objective Response Rate (ORR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response
To evaluate anti-tumor activity of IDE574 of IDE574 in Part 1B Monotherapy Dose expansion based on DOR per RECIST version 1.1.
时间窗: Approximately 24 months total study duration
Duration of response (DOR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response
Safety and tolerability of IDE574 in combination with Fulvestrant in Part 2A Combination Dose Escalation based on incidence of DLT
时间窗: Approximately 24 months total study duration
Incidence of DLT; incidence and severity of AEs/SAEs graded based on CTCAE V6.0
Safety and tolerability of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on the incidence and severity of AEs/SAEs
时间窗: Approximately 24 months total study duration
Incidence and severity of AEs/SAEs graded based on CTCAE V6.0
Anti-tumor activity of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on the ORR per RECIST version 1.1
时间窗: Time Frame: Approximately 24 months total study duration
Objective Response Rate (ORR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response
Anti-tumor activity of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on DOR per RECIST version 1.1.
时间窗: Time Frame: Approximately 24 months total study duration
Duration of response (DOR) per RECIST version 1.1 will be calculated based on the proportion of participants with confirmed Complete Response or Partial Response
次要结局
- Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on the ORR per RECIST version 1.1(Approximately 24 months total study duration)
- Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on DOR per RECIST version 1.1.(Approximately 24 months total study duration)
- Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on Clinical Benefit Rate (CBR)(Approximately 24 months total study duration)
- Evaluate the preliminary antitumor activity of IDE574 in Part 1A Monotherapy Dose Escalation based on Disease control rate(Approximately 24 months total study duration)
- Evaluate the pharmacokinetics (PK) of IDE574 in Part 1A Monotherapy Dose Escalation(Approximately 24 months total study duration)
- Evaluate the PK of IDE574 in Part 1B Monotherapy Dose Expansion(Approximately 24 months total study duration)
- Evaluate antitumor activity of IDE574 in Part 1B Monotherapy Dose Expansion based on CBR for ER+, HER2- breast cancer(Approximately 24 months total study duration)
- Evaluate antitumor activity of IDE574 in Part 1B Monotherapy Dose Expansion based on DCR for other solid tumor types(Approximately 24 months total study duration)
- Evaluate the preliminary antitumor activity of IDE574 in combination with Fulvestrant Part 2A Combination Dose Escalation based on ORR per RECIST version 1.1(Approximately 24 months total study duration)
- Evaluate the preliminary antitumor activity of IDE574 in combination with Fulvestrant Part 2A Combination Dose Escalation based on DOR per RECIST version 1.1(Approximately 24 months total study duration)
- Evaluate the preliminary antitumor activity of IDE574 in combination with Fulvestrant Part 2A Combination Dose Escalation based on CBR per RECIST version 1.1(Approximately 24 months total study duration)
- Evaluate the PK of IDE574 in Part 2A Combination Dose Escalation(Approximately 24 months total study duration)
- Evaluate antitumor activity of IDE574 in combination with Fulvestrant in Part 2B Combination Dose Expansion based on CBR per RECIST version 1.1(Approximately 24 months total study duration)
- Evaluate the PK of IDE574 in Part 2B Combination Dose Expansion(Approximately 24 months total study duration)