NCT04662580进行中（未招募）1 期
A Phase 1, Multicenter, Open-Label, Dose-Escalation, and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of ARX517 as Monotherapy and in Combination With Androgen Receptor Pathway Inhibitors in Subjects With Metastatic Prostate Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 183
- 试验地点
- 19
- 主要终点
- Assess incidence of adverse events
研究概览
简要总结
This is a phase 1 study to assess the safety and tolerability of ARX517 as monotherapy or combination therapy in adult subjects with metastatic prostate cancer (mPC).
详细描述
This is a first-in-human (FIH), Phase 1, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, PK, pharmacodynamic (PDy), and preliminary anti-tumor activity of ARX517 alone, or in combination with androgen receptor pathway inhibitors (ARPIs), in adult subjects with metastatic prostate cancer .
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Male and ≥18 years at the time of providing written informed consent.
- •Histologically confirmed prostate adenocarcinoma.
- •For subjects who have not undergone an orchiectomy, must be undergoing treatment with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist and must agree to continue such therapy while on study treatment. Subjects enrolled to mCRPC cohorts must have serum testosterone levels of ≤50ng/dL (1.73nM at Screening).
- •Must receive prior treatment(s) as defined in the protocol for each cohort
- •Documented evidence of disease progression on or after the most-recent prior regimen for mCRPC cohorts
- •mCSPC combination cohorts: High volume metastatic disease documented by CT/MRI and/or 99mTC bone scan (for bone lesions)
- •Adequate blood counts
- •Must have at least 1 PSMA-positive metastatic lesion and no measurable PSMA-negative lesions by local assessment for alternative dosing regimen and combination cohorts.
排除标准
- •Receipt of chemotherapy within 21 days prior to enrollment; hormonal therapy (not including LHRH analogs) within 7 days prior to enrollment; palliative radiation therapy within 7 days prior to enrollment; or any other anticancer therapy within 21 days prior to enrollment or other therapy for monotherapy cohorts
- •Receipt of more than 1 prior taxane regimen or non-taxane chemotherapy for prostate cancer for alternative dose regimen and mCRPC combination cohorts
- •Receipt prior apalutamide, enzalutamide, or darolutamide, or AAP for mCRPC combination cohorts
- •Receipt any prior chemotherapy or prior ARPI, and must be greater than 90 days of ADT prior to enrollment for mCSPC combination cohorts
- •Use of chronic systemic glucocorticoids equivalent to > 10 mg prednisone daily. Note: short-term administration of systemic corticosteroids > 10 mg prednisone equivalent (e.g., for allergic reactions or management of immune- or infusion-related AEs) is allowed.
- •Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic, untreated CNS metastases are eligible provided they have been clinically stable (neurologically stable and not requiring steroids for at least 28 days prior to enrollment).
- •History of any invasive malignancy (other than primary) within the previous 2 years prior to the enrollment date that requires active therapy or is at high risk of recurrence in the opinion of the investigator.
- •Marked baseline prolongation of QT/QT interval corrected for heart rate (QTc), e.g., a triplicate-average QTc interval > 480 milliseconds (CTCAE Grade 2) using Fridericia's QT correction formula at any time within 28 days before enrollment, ongoing history of CTCAE Grade ≥2 QTc at enrollment, or anticipated need to perform repeat ECG evaluations to satisfy re-treatment criteria.
- •Prior history of interstitial lung disease, pneumonitis, or other clinically significant lung disease within 12 months prior to enrollment date.
- •Clinically significant ocular findings by a qualified ophthalmologist or optometrist including active ocular infections or chronic corneal disorders unless approved by the Medical Monitor.
- •Peripheral neuropathy Grade ≥ 2 within 28 days prior to enrollment.
- •For combination cohorts with apalutamide: no prior history of seizure or condition that may predispose to seizure (including but not limited to prior cerebrovascular accident, TIA or loss of consciousness within the last 12 months, brain AVM, brain metastases).
- •24-hour urine protein > 1g/24h
研究组 & 干预措施
ARX517+AAP
Experimental
ARX517 and abiraterone acetate plus prednisone(AAP)
干预措施: Abiraterone acetate (Drug)
ARX517+Apalutamide
Experimental
ARX517 and apalutamide
干预措施: Apalutamide (Drug)
ARX517+AAP
Experimental
ARX517 and abiraterone acetate plus prednisone(AAP)
干预措施: Prednisone (Drug)
ARX517
Experimental
ARX517 will be administered via intravenous (IV) infusion, with the initial treatment regimen by weight-based infusion at an interval of every 3 weeks. Other treatment regimen may be explored.
干预措施: ARX517 (Drug)
ARX517+Apalutamide
Experimental
ARX517 and apalutamide
干预措施: ARX517 (Drug)
ARX517+AAP
Experimental
ARX517 and abiraterone acetate plus prednisone(AAP)
干预措施: ARX517 (Drug)
结局指标
主要结局
Assess incidence of adverse events
时间窗: 1.5 Years
Incidence and severity of adverse events or serious adverse events of ARX517 alone or in combination with ARPIs will be assessed to determine the safety and tolerability of the treatment using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5 (CTCAE).
次要结局
- Area under the serum concentration-time curve (AUC) for ARX517 alone or in combination with ARPIs(3 Year)
- Maximum serum concentration (Cmax) for ARX517 alone or in combination with ARPIs(3 Year)
- Trough concentration (Ctrough) for ARX517 alone or in combination with ARPIs(3 Year)
- Incidence of ADA against ARX517 alone or in combination with ARPIs(3 year)
- Overall survival (OS)(3 year)
- Assess changes in serum prostate specific antigen (PSA) levels(3 year)
- Progression-free survival (PFS)(3 year)
研究者
研究点 (19)
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