A Phase 1 Study of JNJ-101684362 (HLD-0117) in Patients With Estrogen Receptor Positive (ER+) Metastatic Breast Cancer (MBC)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 170
- 试验地点
- 6
- 主要终点
- Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to find out the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDEs) of JNJ-101684362 (HLD-0117), to evaluate the safety of JNJ-101684362 (HLD-0117) , and how well the participants can tolerate it in Part 1 (dose escalation) of the study.
详细描述
This study is an open-label, dose-escalation and cohort expansion study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of oral single-agent, HLD-0117 in patients with ER+ MBC that have progressed after at least 1 prior systemic line of therapy.
During dose escalation, patients will be enrolled into monotherapy cohorts using a Bayesian optimal interval (BOIN) design. Cohorts will enroll a minimum of three patients, with staggered enrollment between cohorts. Backfilling into dose levels determined to be safe may occur to further characterize tolerability and efficacy.
The purpose of the study is to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDEs) of HLD-0117 as a monotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No masking
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
- •Female (assigned at birth), greater than or equal to (>=) 18 years old, and able to provide informed consent
- •Histologically confirmed metastatic or locally advanced breast cancer
- •Postmenopausal status defined by surgical or natural menopause, or ovarian suppression with a GnRH agonist
- •Prior therapy including
- •Must have received at least one endocrine therapy in the metastatic setting.
- •Must have received at least one cyclin-dependent kinase (CDK) 4/6i, either in the adjuvant and/or metastatic setting.
- •For Part 1 and Part 2 Cohorts 2A, 2B, 2C, and 2D: Participants may have received up to two prior distinct cytotoxic regimens (for example, taxanes, antibody-drug conjugates (ADCs), etc.) in the metastatic setting, unless discussed and approved by the medical monitor.
- •For Part 2 Cohort 2E: Participants must have received more than two prior distinct cytotoxic regimens (for example, taxanes, ADCs, etc.) in the metastatic setting.
- •Radiologic disease progression on the most recent therapy
- •Patients must have disease evaluable per response evaluation criteria in solid tumors (RECIST) v1.1
- •For Part 1 and Part 2B, 2C, and 2E: Participants may have either evaluable or measurable disease per RECIST v1.
- •For Part 2 Cohort 2A: Participants should have measurable soft tissue disease per RECIST v1.
- •For Part 2 Cohort 2D: Participants should have evaluable but not measurable disease.
- •Willingness to provide baseline and on-treatment tumor biopsies, unless not feasible or medically appropriate
- •For Part 1 and Part 2 (all cohorts):
- •Participants must have documented >=10% ER staining and human epidermal growth factor receptor 2 (HER2) negative (per american society of clinical oncology [ASCO] college of american pathologists [CAP] guidelines) on the most recent tumor biopsy sample obtained.
- •For Part 2 Cohort 2B: Participants must have recent estrogen receptor 1 gene (ESR1) wild type from tumor or circulating tumor deoxy ribonucleic acid (ctDNA) testing performed after the most recent endocrine therapy prior to enrollment.
- •For Part 2 Cohort 2C: Participants must have ESR1 mutation detected from tumor or ctDNA testing performed prior to enrollment.
- •Eastern cooperative oncology group (ECOG) performance status 0-1 and life expectancy of at least 3 months
- •Adequate organ function Recovery from prior therapy-related toxicities to Grade <=1 (except alopecia; neuropathy and endocrinopathies <=Grade 2)
- •Ability to swallow oral medication and comply with study procedures
- •Stable dose (>=30 days) of bisphosphonates or denosumab, if applicable
排除标准
- •Participants with Inflammatory breast cancer or leptomeningeal disease or brain metastases, with the exception of patients with definitively treated brain metastases that are clinically stable and asymptomatic for >2 weeks and who are off or receiving low-dose corticosteroid treatment (<=10 mg prednisone or equivalent) for at least 2 weeks prior to start of study treatment.
- •Recent major bleeding or uncontrolled bleeding disorder
- •Ongoing corticosteroid use >10 mg/day (prednisone equivalent)
- •Recent anticancer or investigational therapy within 14 days (28 days for fulvestrant)
- •Untreated or unstable spinal cord compression
- •Significant cardiovascular disease within 6 months or ongoing uncontrolled cardiac conditions
- •Active or uncontrolled infection (controlled HIV or treated hepatitis C allowed)
- •Uncontrolled renal, pancreatic, or liver disease (excluding stable conditions such as Gilbert's syndrome or liver metastases)
- •Another malignancy requiring treatment within 2 years (except low-risk, curatively treated cancers)
- •Major surgery within 28 days
- •Any condition that may interfere with safety or study compliance
- •Pregnancy or breastfeeding
研究组 & 干预措施
Arm 1
JNJ-101684362 (HLD-0117): Participants with estrogen receptor positive (ER+) metastatic breast cancer (MBC) will receive JNJ-101684362 (HLD-0117) orally once daily as monotherapy in Part 1 until recommended dose(s) for expansion has been developed. Participants in Part 2 will receive JNJ-101684362 (HLD-0117) at the RP2Ds developed in Part 1.
干预措施: JNJ-101684362 (HLD-0117) (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLTs)
时间窗: 28 days
Frequency of dose-limiting toxicities (DLTs)
AEs, ECGs, Labs and Clinical Changes
时间窗: 28 days
Frequency and severity of adverse events (AEs) and abnormal electrocardiogram (ECG), laboratory and clinical changes from baseline
次要结局
- Objective response rate (ORR)(56 Days)
- Progression-free survival (rPFS)(56 days)
- Disease Control Rate (DCR)(24 weeks)
- Duration of response (DOR)(28 days)
- Clinical Benefit Rate (CBR)(24 weeks)