An Open-label, Multi-center, First in Human Phase I Global Dose Escalation and Expansion Study of INR731 Single Agent or in Combination With an Androgen Receptor Pathway Inhibitor in Patients With Metastatic Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 208
- 试验地点
- 5
- 主要终点
- Incidence and severity of dose-limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, pharmacokinetics/pharmacodynamics, preliminary anti-tumor activity, and recommended dose of INR731 as a single agent and in combination with standard-of-care androgen receptor pathway inhibitors (ARPIs) in adult patients with metastatic prostate cancer.
详细描述
This is a first-in-human, open-label, phase I, multi-center study which consists of three treatment arms: INR731 single agent (Arm A), and INR731 in combination with enzalutamide (Arm B) or abiraterone (Arm C).
The single agent arm has a dose escalation part followed by a dose expansion part. Once the single agent recommended dose(s) is determined during dose escalation, the study may proceed to dose expansion to further explore safety, tolerability and preliminary anti-tumor activity. The single agent dose expansion part will include a post-standard of care (SOC) metastatic castration resistant prostate cancer (mCRPC) group and patients with time to castration resistance (TTCR) <12 months.
The combination arms have a dose escalation of INR731 in combination with enzalutamide or abiraterone followed by a dose expansion of INR731 in combination with enzalutamide only. The combination dose escalation will be conducted in patients with mCRPC who have progressed following standard of care (post-SOC). During combination escalation, once the safety and tolerability of INR731 with the combination agent(s) is assessed, the study may proceed to dose expansion. The combination dose expansion part will include first-line (1L) mCRPC patients with no prior treatment in the mCRPC setting.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤
- •Participants must have histological and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are eligible as long as the non-adenocarcinoma feature is the minority component.
- •At least 1 metastatic lesion (according to local radiology assessment by the investigator) present on baseline CT, MRI, or bone scan imaging obtained ≤28 days prior to Cycle 1 Day 1 (C1D1).
- •Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L).
- •Ongoing androgen deprivation therapy (ADT) either via orchiectomy and/or ongoing gonadotropin-releasing hormone (GnRH) analog or inhibitor is allowed.
- •Participants must be mCRPC patients who have either progressed on or are not candidates for other SOC. Prior taxane, poly(ADP) ribose polymerase (PARP) inhibitor, and lutetium Lu 177 vipivotide tetraxetan (Pluvicto) are allowed. Combination expansion patients, however, must be 1L mCRPC with no prior treatment in the mCRPC setting. Treatment within the mHSPC setting does not affect eligibility.
排除标准
- •Age < 18 years old.
- •Histological and/or cytological confirmation of non-adenocarcinoma of the prostate.
- •Patients with biochemical recurrence only or those without evidence of metastatic disease by radiographical imaging (CT/MRI or bone scan) are not eligible.
- •Patients previously treated with a cereblon-based degrader.
- •Patients who are HIV+ or immune compromised.
- •Use of agents known to prolong QT interval unless they can be permanently discontinued for the duration of the study
- •Treatment with an investigational agent within 7 days (or 5 half-lives, whichever is longer) of the anticipated Cycle 1 Day 1 (C1D1).
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
INR731 in combination with enzalutamide (Arm B)
The dose escalation part with INR731 in combination with enzalutamide may be followed by a dose expansion part.
干预措施: Enzalutamide (Drug)
INR731 in combination with enzalutamide (Arm B)
The dose escalation part with INR731 in combination with enzalutamide may be followed by a dose expansion part.
干预措施: INR731 (Drug)
INR731 single agent (Arm A)
The dose escalation part with single agent INR731 may be followed by a dose expansion part.
干预措施: INR731 (Drug)
INR731 single agent (Arm A)
The dose escalation part with single agent INR731 may be followed by a dose expansion part.
干预措施: Androgen deprivation therapy (ADT) (Drug)
INR731 in combination with enzalutamide (Arm B)
The dose escalation part with INR731 in combination with enzalutamide may be followed by a dose expansion part.
干预措施: Androgen deprivation therapy (ADT) (Drug)
INR731 in combination with abiraterone (Arm C)
Dose escalation of INR731 in combination with abiraterone.
干预措施: INR731 (Drug)
INR731 in combination with abiraterone (Arm C)
Dose escalation of INR731 in combination with abiraterone.
干预措施: Abiraterone (Drug)
INR731 in combination with abiraterone (Arm C)
Dose escalation of INR731 in combination with abiraterone.
干预措施: Androgen deprivation therapy (ADT) (Drug)
结局指标
主要结局
Incidence and severity of dose-limiting toxicities (DLTs)
时间窗: 28 days
A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 that occurs within the first 28 days and not clearly and incontrovertibly assessed as due to disease progression, intercurrent illness, concomitant medication, or extraneous causes with the exceptions defined in the study protocol. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to approximately 24 months
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and electrocardiograms (ECGs) qualifying and reported as AEs.
Frequency of dose interruptions and reductions
时间窗: Up to approximately 24 months
Number of participants with dose interruptions and/or reductions to assess the tolerability.
Dose intensity
时间窗: Up to approximately 24 months
Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.
次要结局
- Overall Response Rate (ORR)(Up to approximately 24 months)
- Disease Control Rate (DCR)(Up to approximately 24 months)
- Radiological Progression Free Survival (rPFS)(Up to approximately 24 months)
- Prostate-Specific Antigen 50% response rate (PSA50 rate)(Up to approximately 24 months)
- Area under the plasma concentration-time curve (AUC) of INR731(From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.)
- Maximum plasma concentration (Cmax) of INR731(From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.)
- Time to reach maximum plasma concentration (Tmax) of INR731(From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.)
- Trough concentration (Ctrough) of INR731(From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.)
- Plasma concentrations of study drugs(From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.)
- Progression Free Survival (PFS)(Up to approximately 24 months)