NCT03118349终止1 期
Phase I, Open-Label, Multi-Center, Dose Escalation With Expansion Trial of 177Lu Human Monoclonal Antibody 5B1 (MVT-1075) in Combination With a Blocking Dose of MVT-5873 as Radioimmunotherapy in Relapse/Refractory Subjects With Pancreatic Cancer or Other CA19-9 Positive Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Occurrence of graded adverse events (AEs) in each subject
研究概览
简要总结
Open label, nonrandomized, dose-escalation with cohort expansion study of MVT-5873/MVT-1075 in subjects with previously treated, Carbohydrate Antigen 19-9 (CA19-9) positive malignancies (e.g., pancreatic adenocarcinoma).
详细描述
Open label, nonrandomized, dose escalation study of MVT-5873/MVT-1075 to evaluate safety, dosimetry, determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and define the pharmacokinetics of MVT-1075. The population consisted of subjects with CA19-9 positive malignancies (i.e., predominately pancreatic adenocarcinoma) who may benefit from a CA19-9-based radioimmunotherapy.
The study utilized a 3+3 study design to identify the MTD. The RP2D was planned to be no higher than the MTD. An expansion group was planned to receive MVT-5873/MVT-1075 at the RP2D in order to obtain initial estimates of response and additional information on safety.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Signed, informed consent
- •Age 18 or more years
- •Histologically or cytologically confirmed, previously treated, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other CA19-9 positive malignancies
- •Prior treatment with (or intolerance to) at least one standard systemic regimen for the patient's respective tumor
- •Evidence of tumor expression of CA19-9 based on immunohistochemistry performed on tumor samples or elevated serum levels (≥1.5 x upper limits of normal [ULN]) of CA19-9 considered secondary to tumor
- •Evaluable or measurable disease based on RECIST 1.1
- •Recovered from any prior treatment related toxicity to at least Grade 1 with exception of Grade 2 alopecia or other Grade 2 toxicity with prior approval of the Medical Monitor
- •If previously exposed to irradiation, the combined prior and anticipated exposure for Cycle 1 is not expected to exceed organ exposure limits outlined in the study protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or Karnofsky performance status (KPS) of 100% to 80%
- •Adequate hematologic, renal and hepatic laboratory parameters
- •Willingness to participate in collection of pharmacokinetic samples
- •Willingness to use adequate contraception throughout study and for a period of 3 months after last dose of MVT-5873 or MVT-1075 (whichever is later)
排除标准
- •Brain metastases unless previously treated and well controlled for at least 3 months
- •Any tumor mass greater than 10 cm in longest diameter
- •Other known active cancer(s) likely to require treatment in the next two years
- •Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- •Prior radiation therapy encompassing more than 25% of the skeleton or prior treatment with 89Strontium or 153Samarium
- •Fewer than 28 days from prior anticancer therapy including chemotherapy, hormonal, investigational, and/or biological therapies and irradiation except for:
- •Ongoing hormonal therapy administered for control of cancer (e.g., breast cancer, prostate cancer), which may be continued throughout the study
- •MVT-5873 and MVT-2163 administered as part of a different protocol
- •Major surgery other than diagnostic surgery within 28 days of Study Day 1
- •History of anaphylactic reaction to human, or humanized, antibody
- •Pregnant or currently breast-feeding
- •Known to be positive for human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C
- •Psychiatric illness/social situations that would interfere with compliance with study requirements
- •Significant cardiovascular risk including, but not limited to, recent (within 4 weeks) coronary stenting or myocardial infarction within 6 months
研究组 & 干预措施
Escalation Cohorts
Experimental
MVT-5873 blocking dose and MVT-1075 dose escalation; Initial to maximum tolerated dose
干预措施: MVT-1075 (Drug)
Escalation Cohorts
Experimental
MVT-5873 blocking dose and MVT-1075 dose escalation; Initial to maximum tolerated dose
干预措施: MVT-5873 (Drug)
Expansion Cohort - no subjects enrolled
Experimental
MVT-5873 blocking dose and MVT-1075 Maximum tolerated dose
干预措施: MVT-1075 (Drug)
Expansion Cohort - no subjects enrolled
Experimental
MVT-5873 blocking dose and MVT-1075 Maximum tolerated dose
干预措施: MVT-5873 (Drug)
结局指标
主要结局
Occurrence of graded adverse events (AEs) in each subject
时间窗: Through study completion. Estimated at one year
Occurrence of graded AEs in each subject
The MTD of MVT-5873/MVT-1075
时间窗: Through study completion. Estimated at one year
The MTD of MVT-5873/MVT-1075 is the highest dose of MVT-1075 at which fewer than 33% subjects experience a dose limiting toxicity
次要结局
- Specific organ distribution of MVT-1075 as assessed with single-photon emission computed tomography (SPECT) imaging(Through study completion. Estimated at one year)
- Specific organ distribution of MVT-1075 as assessed with planar gamma camera(Through study completion. Estimated at one year)
- A RP2D of MVT-5873/MVT-1075(Through study completion. Estimated at one year.)
- Cmax(Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).)
- Evaluate duration of response of MVT-5873/MVT-1075(Through study completion. Estimated at one year.)
- Evaluate the tumor response rate to MVT-5873/MVT-1075 at the RP2D(Through study completion. Estimated at one year.)
- Cmin(Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).)
- Vd(Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).)
- t1/2(Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).)
- Evaluate formation of anti-drug antibodies (ADA)(On Day 1, Day 15 and End of Treatment Visit only of each cycle for up to 4 cycles. (each cycle is 57 days))
- Tmax(Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).)
- AUC(Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).)
- Cl(Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).)
研究者
研究点 (2)
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