An Open-label Phase 1b Study of E7090 Monotherapy and in Combination With Other Anticancer Agents in Subjects With ER+, HER2- Recurrent/Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 22
- 主要终点
- Part 1: Recommended Dose (RD) of E7090 in Combination With Other Anticancer Agents
研究概览
简要总结
The primary purpose of this study is to evaluate the tolerability and safety of E7090 as monotherapy and in combination with other anticancer agents in participants with ER+, HER2- recurrent/metastatic breast cancer and to determine the recommended dose (RD) of E7090 in combination with other anticancer agents for subsequent phase studies.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Common to Part 1, 2 and 3
- •Participants who provided written voluntary informed consent for participation in the study.
- •Female participants who are age >=18 years at the time of informed consent.
- •Post-menopausal or pre/peri-menopausal participants who have been continuously on concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist since before the start of study treatment and is planned to continue this treatment during the study.
- •Participants with histologically confirmed diagnosis of progressive/recurrent or metastatic, ER+, HER2 negative breast cancer.
- •Participants who received prior CDK4/6 inhibitor treatment.
- •Participants with Performance Status (PS) score of 0-1 established by Eastern Cooperative Oncology Group (ECOG).
- •Part 1 and Part 2: Participants with at least one accessible lesion for biopsy and who agree to undergo a biopsy of accessible lesion prior to study treatment (if archived tissues collected after CDK4/6 inhibitor treatment is not available) and on Day 1 of Cycle
- •(Part 3) participants must agree to undergo a biopsy at screening if no archival tissue is available (tissue collection must be after CDK4/6 inhibitor treatment and prior to study treatment). A biopsy on Day 1 of Cycle 3 is not mandatory.
- •Participants who agree to provide archival or fresh tumor tissue collected after CDK4/6 inhibitor treatment.
- •Part 2 only: Participants with positive protein expression of fibroblast growth factor receptor 1 (FGFR) and/or FGFR2, with which tumor was collected after CDK4/6 inhibitor treatment at the central laboratory.
排除标准
- •Participants with brain or subdural metastases, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (example. radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
- •(Part 1 and Part 2) Participant who have received 2 or more regimen of chemotherapy for the treatment of advanced or metastatic lesions.
- •(Part 3) Participant who have received 1 or more regimens of chemotherapy or antibody-drug conjugate therapy for the treatment of advanced or metastatic lesions.
- •Participant with inflammatory breast cancer.
- •Participant with bilateral breast cancer of different histologic types. Participants who have bilateral breast cancers that are both ER+ and HER2- may be enrolled in the study.
- •Participant who have history of active malignancy within the past 24 months prior to the first dose of study drugs.
- •Participants with clinically significant cardiovascular impairment.
- •Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
- •Concomitant active infection requiring systemic treatment.
- •Participants who test positive for human immunodeficiency virus (HIV antibody), or positive for hepatitis B surface (HBs antigen) or hepatitis C (HCV antibody and RNA).
- •Participants with following ocular disorders:
- •Current evidence of Grade 2 or higher corneal disorder.
- •Current evidence of active retinopathy (example. age-related macular degeneration, central serous chorioretinal disease, retinal tear)
- •Participants who received prior treatment with an FGFR inhibitor.
- •Females who are pregnant or breastfeeding.
- •Part 1 only: Participants with T-score less than (<) -2.5 by dual-energy X-ray absorptiometry (DXA) scan.
- •Part 3 only: Participants who received 3 or more prior lines of endocrine therapy in advanced/metastatic setting.
研究组 & 干预措施
Part 1 Dose Escalation: E7090 + Fulvestrant or Exemestane
Participants will receive E7090 tablets, orally, once daily along with fulvestrant 500 milligram (mg), intramuscular injection on Days 1 and 15 of Cycle 1 and each Day 1 of cycle 2 or later, or along with exemestane 25 mg tablet, orally, once daily in 28 days cycle. Each cycle length equals to (=) 28 days.
干预措施: E7090 (Drug)
Part 1 Dose Escalation: E7090 + Fulvestrant or Exemestane
Participants will receive E7090 tablets, orally, once daily along with fulvestrant 500 milligram (mg), intramuscular injection on Days 1 and 15 of Cycle 1 and each Day 1 of cycle 2 or later, or along with exemestane 25 mg tablet, orally, once daily in 28 days cycle. Each cycle length equals to (=) 28 days.
干预措施: Exemestane (Drug)
Part 1 Dose Escalation: E7090 + Fulvestrant or Exemestane
Participants will receive E7090 tablets, orally, once daily along with fulvestrant 500 milligram (mg), intramuscular injection on Days 1 and 15 of Cycle 1 and each Day 1 of cycle 2 or later, or along with exemestane 25 mg tablet, orally, once daily in 28 days cycle. Each cycle length equals to (=) 28 days.
干预措施: Fulvestrant (Drug)
Part 3 Dose Expansion: E7090 + Fulvestrant
Participants will receive E7090 tablets, orally, once daily along with fulvestrant 500 mg, intramuscular injection on Days 1 and 15 of Cycle 1 and each Day 1 of cycle 2 or later. Each cycle length =28 days.
The dose of E7090 for Part 3 in combination with fulvestrant will be determined based on the safety, tolerability, pharmacokinetic (PK), and biomarker data obtained from Part 1.
干预措施: E7090 (Drug)
Part 2 Monotherapy: E7090
Participants will receive E7090 tablets, orally, once daily in 28 days cycle. Each cycle length =28 days.
干预措施: E7090 (Drug)
Part 3 Dose Expansion: E7090 + Fulvestrant
Participants will receive E7090 tablets, orally, once daily along with fulvestrant 500 mg, intramuscular injection on Days 1 and 15 of Cycle 1 and each Day 1 of cycle 2 or later. Each cycle length =28 days.
The dose of E7090 for Part 3 in combination with fulvestrant will be determined based on the safety, tolerability, pharmacokinetic (PK), and biomarker data obtained from Part 1.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Part 1: Recommended Dose (RD) of E7090 in Combination With Other Anticancer Agents
时间窗: Up to Cycle 1 (each cycle length = 28 days)
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: Up to Cycle 1 (each cycle length = 28 days)
DLTs will be assessed based on combination regimen-related adverse events (AEs) occurred during Cycle 1 of Part 1 and the severity of AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 30 days after last administration of study drug (approximately up to 66 months)
Safety assessments will consist of monitoring and recording all AEs and SAEs; regular measurement of vital signs and ECG; and regular monitoring of clinical laboratory parameters, body weight and bone density.
次要结局
- Cmax: Maximum Observed Plasma Concentration of E7090, its Metabolite (M2) and Exemestane(For E7090 and its metabolite (M2)- Parts 1 and 2 Cycle 1 Day 1: 0-24 hours post-dose; For exemestane- Part 1 Cycle 1 Day 1: 0-24 hours post-dose (each cycle length = 28 days))
- AUC: Area Under the Plasma Concentration-time Curve of E7090, its Metabolite (M2) and Exemestane(For E7090 and its metabolite (M2)- Parts 1 and 2 Cycle 1 Day 1: 0-24 hours post-dose; For exemestane- Part 1 Cycle 1 Day 1: 0-24 hours post-dose (each cycle length = 28 days))
- Part 1: Plasma Concentration of Fulvestrant(Cycles 2 and 3 Day 1: pre-dose (each cycle length = 28 days))
- Objective Response Rate (ORR)(Baseline up to 66 months)
- Disease Control Rate (DCR)(Baseline up to 66 months)
- Clinical Benefit Response (CBR)(Baseline up to 66 months)
- Progression-free Survival (PFS)(Baseline up to 66 months)
- Overall Survival (OS)(Baseline up to 66 months)
- Time to Response (TTR)(Baseline up to 66 months)
- Duration of Response (DOR)(Baseline up to 66 months)