A Phase 1/2 Trial of ADI-212 (Engineered γδ Chimeric Antigen Receptor [CAR] Vδ1 T Cells Targeting PSMA) in Adults With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- The incidence of Subjects with Dose Limiting Toxicity within each dose level
研究概览
简要总结
This is a Phase 1/2 multicenter, open-label, dose finding and dose expansion study of ADI-212 in participants with metastatic castration-resistant prostate cancer (mCRPC)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Histologic and/or cytologic confirmation of adenocarcinoma of the prostate
- •Documented evidence of metastatic disease.
- •Target lesions must be PSMA-avid by PET/CT, based on local determination.
- •Must have castration testosterone level (< 50 ng/dL) and must remain on androgen deprivation therapy (ADT) to maintain this level.
- •Progressive mCRPC based on at least one of the following:
- •PSA progression defined as two increases in PSA measured at least one week apart
- •Soft-tissue progression defined per PCWG3
- •Bone disease progression defined per PCWG3
- •Evaluable target lesions, per PCWG3
- •ECOG of 0 or 1
- •Prior therapy :
- •Participants must have progressed after at least two prior courses of systemic ADT.
- •Participants may have had no more than one course of prior taxane therapy.
- •Prio PSMA-targeted radioligand therapy (e.g., Pluvicto) is permitted.
- •Prior PARP inhibitor therapy is permitted.
- •Must have prior therapy washout, including investigational agents, of at least three weeks for prior systemic therapies other than androgen deprivation therapies, or five half-lives if the duration is shorter than three weeks.
- •Adequate BP, hematological, and organ function
排除标准
- •Prior radiation therapy within 21 days prior to start of study treatment
- •Prior positive superscan results [i.e.: an imaging appearance on a Tc-99m diphosphonate bone scan]
- •Current or history of any of the following conditions or treatments:
- •Presence of known central nervous system (CNS) metastases
- •History of clinically significant infection
- •Active malignancy within the past 24 months
- •Any other condition requiring treatment with a prohibited medication, as specified in the protocol
- •Prior treatment with gene therapy, genetically modified cell therapy, or adoptive T cell therapy
- •Prior PSMA-targeted therapies other than a single course of a PSMA-targeted radioligand therapy
- •Prior CAR-T therapy
- •Clinically significant cardiovascular disease
- •Prior solid organ transplant
- •Unwilling to participate in an extended safety monitoring period
- •Any medical condition or clinical laboratory abnormality likely to interfere with assessment of safety or efficacy of study treatment
研究组 & 干预措施
Dose Expansion
Dose Expansion to assess the anti-tumor responses to ADI-212 at the recommended Phase 2 dose (Part 2)
干预措施: ADI-212 (Drug)
Dose Escalation
ADI-212 is administered via infusion using the 3 + 3 design starting with three planned dose levels to determine the maximum tolerated dose (MTD or maximum assessed dose (MAD)
干预措施: ADI-212 (Drug)
Dose Expansion
Dose Expansion to assess the anti-tumor responses to ADI-212 at the recommended Phase 2 dose (Part 2)
干预措施: Fludarabine (Drug)
Dose Escalation
ADI-212 is administered via infusion using the 3 + 3 design starting with three planned dose levels to determine the maximum tolerated dose (MTD or maximum assessed dose (MAD)
干预措施: Fludarabine (Drug)
Dose Expansion
Dose Expansion to assess the anti-tumor responses to ADI-212 at the recommended Phase 2 dose (Part 2)
干预措施: Cyclophosphamide (Drug)
Dose Escalation
ADI-212 is administered via infusion using the 3 + 3 design starting with three planned dose levels to determine the maximum tolerated dose (MTD or maximum assessed dose (MAD)
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
The incidence of Subjects with Dose Limiting Toxicity within each dose level
时间窗: Day 42
The primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed Dose (MAD) and Recommended Phase 2 Dose (RP2D)
Proportion of treatment emergent and treatment related Adverse Events
时间窗: 2 years
This primary endpoint will be used to determine Overall Response Rate (ORR) per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 per local assessment and Radiographic progression-free survival (rPFS)
次要结局
未报告次要终点