An Open Label, Multicenter, Safety and Efficacy Phase 2 Study of PRL3-Zumab in Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
This is a multicenter, Phase II, open-label, single-dose level (6 mg/kg) study of PRL3-zumab monotherapy in patients with unresectable or metastatic solid tumors.
The study consists of a screening period (Day -21 to Day -1, during which all screening assessments must be completed prior to the first administration of study treatment), a treatment period (study visits every 2 weeks), an End-of-Treatment (EOT) visit (to beconducted within 14 days after discontinuation of treatment for any reason), a safety follow up visit (30 days after the last dose of study treatment), and survival follow-up (every 3 months after treatment discontinuation via telephone or other appropriate methods until the data cutoff date). PRL3-zumab will be administered via intravenous (i.v.) infusion until patients meet discontinuation criteria (clinically determined disease progression or disease progression confirmed according to RECIST v1.1 and iRECIST, intolerable toxicity, or withdrawal of consent). One treatment cycle is defined as 4 weeks (two infusions given 2 weeks apart).
Patients will undergo safety assessments, including laboratory tests, prior to each infusion within each cycle.
Tumor assessments will be performed at baseline according to RECIST v1.1 and iRECIST and every 8 weeks after initiation of study treatment. Quality of life (QoL) will be assessed at screening and every 8 weeks during treatment. Study treatment will be discontinued if patients develop clinically determined disease progression, disease progression per RECIST v1.1 and iRECIST, intolerable toxicity, or withdraw consent. The EOT visit will be conducted within 14 days after the last dose of study treatment.
For the intensive PK sampling subgroup (N = 10), pharmacokinetic assessments will be performed at the following time points: Cycle 1 Day 1 (pre-dose, end of infusion, 2 and 6 hours post-infusion), Cycle 1 Day 2 (24 hours post-infusion), Cycle 1 Day 6 (120 hours post infusion), Cycle 1 Day 10 (216 hours post-infusion), Cycle 1 Day 15 (pre-dose), Cycle 2 Day 1 (pre-dose), Cycle 2 Day 15 (pre-dose), Cycle 3 Day 1 (pre-dose), Cycle 3 Day 15 (pre-dose, end of infusion, 2 and 6 hours post-infusion), Cycle 3 Day 16 (24 hours post infusion), Cycle 3 Day 20 (120 hours post-infusion), Cycle 3 Day 24 (216 hours post infusion), Cycle 4 Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose), Cycle 6 Day 1 (pre-dose), and End of Treatment.
For the sparse PK sampling subgroup (N = 10), PK assessments will be performed at Cycle 1 Day 1 (pre-dose and end of infusion), Cycle 1 Day 15 (pre-dose), Cycle 2 Day 1 (pre-dose and end of infusion), Cycle 3 Day 1 (pre-dose and end of infusion), and End of Treatment Immunogenicity assessments will be performed prior to dosing on Cycle 1 Day 1 and prior to infusion in Cycles 2, 4, and 6. Thereafter, if the patient continues treatment, immunogenicity assessments will be conducted every 3 cycles.
详细描述
Efficacy:
Efficacy assessment will be performed using RECIST 1.1 and iRECIST criteria by the investigator (Figure 12). The tumor evaluation will be performed at baseline (within 14 days) before Cycle 1, Day 1 (C1D1) and for every 56 calendar days from Day 1 of the treatment with contra enhanced computed tomography (CT) scans starting from day 1 of study treatment. Magnetic resonance imaging may be used if patient is not eligible for CT scan.
Same modality of imaging will be used throughout study period.
Safety:
Patient safety will be evaluated based on physical examination, vital signs (blood pressure [systolic and diastolic], heart rate, respiratory rate, and temperature), clinical laboratory tests (hematology, clinical chemistry, coagulation) and adverse events per CTCAE v5. Patient safety will be assessed on an ongoing basis during each cycle.
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
- •Men and women aged 18 or older with unresectable or metastatic solid tumors
- •Patients with locally advanced or metastatic solid tumors who have failed standard therapy or for whom no standard therapy is available. Treatment failure is defined as disease progression during or after systemic antitumor therapy (including but not limited to chemotherapy, radiotherapy, biologic therapy, immunotherapy, and endocrine therapy), or intolerance to treatment-related toxicities. Disease progression must be documented by radiographic evidence or clinical evidence. For patients who have received adjuvant or neoadjuvant therapy (radiotherapy or chemoradiotherapy), disease progression occurring during treatment or after completion of such therapy will be considered treatment failure.
- •Willing to provide written informed consent for the study.
- •Histopathological diagnosis and metastatic status cancer at study entry.
- •Must have received no more than 3 prior lines of treatment for metastatic disease.
- •Life expectancy of more than 6 months
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or
- •Patient should have recovered from toxicity of prior treatment regimen to Grade 1 level except for alopecia or peripheral neuropathy or fatigue as defined by Common Terminology Criteria for Adverse Events (CTCAE version
- •Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at study entry and must follow highly effective contraception
- •WOCBP must be willing to use highly effective methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide,) for the duration of the study and 90 days thereafter.
- •Male participants should take precaution to avoid pregnancy in sexual partner during the study and 90 days thereafter.
- •Adequate organ and hematological function as evidenced by the following laboratory studies within 10 days of treatment:
- •Absolute neutrophil count ≥ 1.0 x 109/L to 8.0 × 10⁹/L.
- •Lymphocyte count ≥ 0.9 × 10⁹/L
- •Platelet count ≥ 75 x 109/L.
- •Hemoglobin ≥ 9 g/dL.
- •Prothrombin time and activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range.
- •Total bilirubin ≤ 1.5x ULN.
- •Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN in the presence of liver metastases).
- •For patients with hepatocellular carcinoma (HCC) Child Pugh score of ≤ B
- •Creatinine < 1.5x ULN. Creatinine clearance (according to Cockcroft-Gault Equation or by 24-hour urine collection) of > 60 mL/min at study entry.
- •According to RECIST 1.1 and iRECIST, patients mush have at least one measurable lesion that meets the following criteria: Accurately measureable at baseline. Longest diameter ≥10mm at baseline (for lymph nodes, short axis ≥ 15mm). Measurable by a reproducible imaging method such as computed tomography (CT) or magnetic resonance imaging (MRI). If only one measurable lesion is present, it must not have been previously treated with local therapy such as radiotherapy.
排除标准
- •Patient has known untreated or symptomatic central nervous system metastasis.
- •Female patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and for 150 days (for pregnancy or conception) or 30 days (for breastfeeding) after the last dose of study treatment.
- •Patient with any of the following virologic findings:
- •Positive hepatitis B surface antigen (HBsAg) and positive HBV DNA
- •Positive anti-HIV antibody and positive HCV RNA
- •Positive HIV antibody
- •Patients with active autoimmune disease requiring systemic treatment, or with a history of autoimmune disease that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis), or patients at high risk (e.g., prior organ transplantation requiring immunosuppressive therapy).
- •Patient is receiving systemic glucocorticoids (only if higher than 10 mg or equivalent of prednisolone daily) or other immunosuppressive treatment for autoimmune disease or any other medical condition.
- •Patient has experienced a severe hypersensitivity reaction to another monoclonal antibody.
- •Patient has received treatment with any systemic anti-cancer therapies within 3 weeks prior to starting study treatment.
- •Patient has undergone radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study treatment.
- •Patient has received > 3 lines of prior systemic chemotherapy for metastatic disease (adjuvant or neoadjuvant chemotherapy treatment completed at least 1-year prior is not to be included in this).
- •Patient is unable to provide informed consent.
- •Patient has a history of another active cancer (which requires treatment and not considered cured by the investigator) within the last 2 years.
- •Patient has received a prior stem cell or bone marrow transplant.
- •Patient has received a live vaccine within 12 weeks of the first dose of PRL3-zumab. (Seasonal influenza vaccines that do not contain live virus are permitted).
- •Patient is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks prior to the anticipated first dose of study treatment in this study.
- •Patients with spinal cord compression caused by tumor, unless the condition has been treated and clinically stable for more than 1 month.
- •Patients with any unstable medical condition or any other disease that may compromise their safety or compliance with the study, including any severe or uncontrolled systemic disease such as uncontrolled hypertension, uncontrolled diabetes mellitus, or active bleeding.
- •Patients with alcohol dependence or a history of drug abuse or substance abuse within 1 year prior to study entry.
- •Patients with any other severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality, that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results.
- •Patients who, in the investigator's judgment, are not suitable for participation in this study.
研究组 & 干预措施
PRL3-zumab treated arm
6mg/kg of PRL3-zumab will be administered
干预措施: PRL3-ZUMAB (Biological)
结局指标
主要结局
Progression free survival (PFS)
时间窗: Time Frame: From the date of first dose of study drug until first documented disease progression or date of death from any cause, whichever comes first, assessed up to 12 months.
PFS is defined as the time from the initiation of study treatment to the date of disease progression as per RECIST v1.1 and iRECIST criteria.
Time to Progression (TTP)
时间窗: From the date of first dose of study drug until first documented disease progression, assessed up to 12 months.
TTP is defined as the time from the the initiation of study treatment to the date of disease progression as per RECIST v1.1 and iRECIST criteria which does not include deaths.
次要结局
- Clinical benefit rate (CBR)(Time Frame: From date of first dose of study drug until first documented disease progression or date of death, whichever comes first, assessed at every 8 weeks up to 48 weeks.)
- Objective Response Rate (ORR)(Time Frame: From date of first dose of study drug until first documented disease progression or date of death, whichever comes first, assessed at every 8 weeks up to 48 weeks.)