An Open-label, Phase I Dose-escalation and Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of Pegylated Arginine Deiminase Dimer (PA5) Injection in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 49
- 试验地点
- 2
- 主要终点
- Incidence of dose limiting toxicity (DLT)
研究概览
简要总结
The goal of this clinical trial is to learn if PA5 is safe and works to treat advanced solid tumors in adults. It will also learn about the tolerability and PK/PD profile of PA5. The main questions it aims to answer are:
- Is intravenous infusion of PA5 monotherapy safe and tolerable for patients with advanced/metastatic solid tumors?
- What is the maximum tolerated dose (MTD) and recommended dose for Phase II clinical trials (RP2D) of PA5 monotherapy?
In the escalation phase, participants will receive PA5 via intravenous infusion on Day 1 of Cycle 1 (28-day cycle). If no dose-limiting toxicity (DLT) occurs, treatment continues from Cycle 2 onward with adjusted frequency (every 2-4 weeks).
In the expansion phase, participants will receive PA5 with the frequency determined based on the results of the escalation phase.
详细描述
This is an open-label, single-arm Phase I clinical study evaluating dose escalation and expansion of PA5 monotherapy in patients with advanced solid tumors. The study consists of two parts: a dose escalation phase to determine the safety, tolerability, and PK/PD profile of PA5, and a dose expansion phase to further assess its safety, pharmacodynamics, and efficacy. The study aims to define the effective dose range for PA5 monotherapy and provide a basis for future Phase II studies (monotherapy or combination therapy). A total of 31-49 participants will be enrolled (13-25 in escalation, 18-24 in expansion).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years, male or female.
- •Patients with histologically or cytologically confirmed advanced/metastatic solid tumors that are unresectable, stage III or IV, have failed standard therapy, are intolerant to standard therapy, have no standard therapy available, or unable to benefit from standard therapy.
- •At least one evaluable lesion (dose escalation phase) or at least one measurable lesion (dose expansion phase) according to RECIST v1.1 criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Expected life expectancy of at least 12 weeks.
- •Brain metastases must be well-controlled and without epileptic symptoms.
- •Participants must have adequate organ and bone marrow function.
排除标准
- •Participants who have received chemotherapy, targeted therapy, anti-tumor Chinese herbal medicine, or palliative care within 2 weeks or 5 half-lives (whichever is longer) prior to the initiation of study treatment; or major surgery, radiotherapy, immunotherapy, or participation in another clinical trial within 4 weeks or 5 half-lives (whichever is longer); or live virus vaccination within 4 weeks or inactivated vaccination within 2 weeks prior to initiation of study treatment.
- •Presence of pleural effusion or ascites requiring clinical intervention (except for participants not requiring drainage or with stable effusion for ≥2 weeks after drainage); presence of pericardial effusion (except for minimal, stable effusion for ≥2 weeks).
- •Toxicities from prior anti-tumor therapy have not recovered to ≤ Grade 2 per NCI-CTCAE v5.0 (excluding toxicities judged by the investigator to pose no safety risk, such as alopecia).
- •Participants taking drugs known to prolong the QTc interval or with risk factors for QTc interval prolongation.
- •Clinically significant active bacterial, fungal, or viral infection.
- •Other malignancies besides the indication under study, either currently or in the past, except for: cured cervical carcinoma in situ (stage IB or lower), non-invasive basal cell or squamous cell skin cancer, malignant melanoma with complete remission (CR) >10 years, or other malignancies with CR >5 years.
- •Pregnant or breastfeeding women.
- •History of allergy to polyethylene glycol compounds.
- •Prior treatment with ADI-PEG20 or other drugs of the same class.
- •The investigator believes the subject is unsuitable for participating in this clinical study.
研究组 & 干预措施
PA5
In the escalation phase, participants will receive PA5 via intravenous infusion on Day 1 of Cycle 1 (28-day cycle). If no dose-limiting toxicity (DLT) occurs, treatment continues from Cycle 2 onward with adjusted frequency (every 2-4 weeks) at dose escalation levels of 0.1, 0.2, 0.4, 0.8, or 1.2 mg/kg.
In expansion phase, participants will receive PA5 via intravenous infusion with the frequency determined based on the results of the escalation phase.
干预措施: PA5 (Biological)
结局指标
主要结局
Incidence of dose limiting toxicity (DLT)
时间窗: At the end of Cycle 1 (each cycle is 28 days)
The maximum tolerated dose (MTD)
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Adverse Events (AEs)
时间窗: From Day 1 of Cycle 1 to Day 28 of Cycle 7 (each cycle is 28 days) or to the end of the treatment (whichever occurs earlier)
including the incidence of overall and categorized AEs, severity (graded according to NCI CTCAE v5.0), seriousness, relationship to PA5 treatment, duration, and outcome.
Recommended phase 2 dose (RP2D) of PA5
时间窗: On Day 28 of Cycle 7 (each cycle is 28 days) or at the end of the treatment (whichever occurs earlier)
Determine RP2D based on the efficacy and safety of PA5 during the dose escalation and expansion phases
次要结局
未报告次要终点