Study to Assess the Safety, Tolerability, and Pharmacokinetics of AMP-224 in Patients With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 4
- 主要终点
- Number of participants with adverse events.
研究概览
简要总结
This is a Phase 1, open-label, multi-center, first time in human study of AMP-224 in adult patients with cancer that is not responding to standard therapy. This study will be conducted in two stages consisting of a Dose-Escalation stage and an Expansion Stage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Must be able to provide informed consent
- •In Dose-Escalation: Must have solid tumor malignancy or cutaneous T-cell lymphoma that has relapsed and is refractory to standard therapy, or for which no standard therapy exists
- •In Expansion Phase: Must have melanoma or ovarian cancer that is histologically or cytologically confirmed
- •Ovarian cancer patients must have recurrent of persistent non-mucinous disease, and must not have received more than 2 prior chemotherapeutic regimens
- •Melanoma patients must have recurrent or persistent non-ocular AJCC Stage IIIC or IV disease that is surgically incurable and unresectable
- •Melanoma patients with documented BRAF mutation that is known to be responsive to BRAF inhibitors must have failed or be intolerant to such inhibitors
- •Must have measurable disease
- •Must be able to provide access to archival (Dose-Escalation Phase) and/or fresh tumor tissue (Dose-Escalation and Expansion Phases) at Screening prior to study entry
- •Must by at least 18 years old
- •Must have adequate organ function
排除标准
- •Prior cancer therapies must have completed at least 14 days or 5 half-lives (whichever is longer) prior to first dose of AMP-224
- •Prior treatment with an anti-PD1 antibody therapy
- •Known antibody response against prior antibody therapy or fusion protein therapeutics
- •Major surgery within 4 weeks prior to first dose of AMP-224
- •Prior allogeneic or autologous bone marrow or organ transplantation
- •Known and/or a history or evidence of autoimmune disease except vitiligo, resolved childhood asthma and stable hypothyroidism
- •Received an immunomodulatory drug within 2 weeks of first dose of AMP-224
- •Active infections requiring antibiotics, physician monitoring, or recurrent fevers >100.4 degrees fahrenheit associated with a clinical diagnosis of active infection
- •Patients with cirrhosis
- •Clinically significant cardiac or electrocardiogram abnormalities
- •History or evidence of HIV
- •Active viral disease (except when the viral infection is associated with the malignancy)
- •Regular use of illicit drugs or a recent history of substance abuse
- •Pregnant or breastfeeding women
研究组 & 干预措施
Stage 1
Stage 1 will identify the recommended Stage 2 dose using a dose-escalation process. Dose-escalation will continue until either a maximum tolerated dose is established, or a therapeutic dose is reached.
干预措施: AMP-224 (Drug)
Stage 2
Stage 2 will further explore the safety, pharmacokinetics, and preliminary clinical activity of AMP-224 in at least one tumor type based on pharmacodynamic assessments and clinical activity emerging from the Dose-Escalation Phase. Tumor tissue and blood specimens will be evaluated for pharmacodynamic markers/activity at specified timepoints throughout the study.
干预措施: AMP-224 (Drug)
结局指标
主要结局
Number of participants with adverse events.
时间窗: From start of study drug administration until the date of first documented progression or date of death from any cause; through Day 56 of final cycle.
Number of participants with dose-limiting toxicities.
时间窗: From start of study drug administration until the date of first documented progression or date of death from any cause: through Day 56 of the final cycle.
Number of participants with changes in laboratory values, vital signs, physical exam, and electrocardiogram.
时间窗: From start of study drug administration until the date of first documented progression or date of death from any cause: through Day 56 of the final cycle.
Determine Maximum Tolerated Dose based on the occurrence of dose-limiting toxicities.
时间窗: From start of study drug administration through Day 28 of Cycle 1.
Determine Recommended Phase 2 Dose following analysis of adverse events, pharmacokinetics and changes in laboratory evaluations.
时间窗: From start of study drug administration until withdrawal; through Day 56 of final cycle.
次要结局
- Evaluate pharmacokinetics, including area under the plasma concentration versus time curve (AUC), peak plasma concentration (Cmax) and clearance of AMP-224 following single and repeat doses of AMP-224.(From Day 0 pre-dose through Day 56 of final cycle.)
- Evaluate Overall Response Rate (ORR), including Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progression-Free Survival (PFS).(From Screening through 12 weeks following final cycle.)
- Characterization of the effects of AMP-224 on its receptor, PD-1, in peripheral T cells via flow cytometry and correlate with response to treatment.(From Screening until 12 weeks post-final cycle.)
- Evaluation and correlation between response to treatment and expression of PD-1 on tumor infiltrating T cells or in available malignant pleural effusions via flow cytometry and/or immunohistochemistry.(Screening through 12 weeks post-final cycle.)
- Evaluation and correlation between response to treatment and expression of B7-H1 on tumors via immunohistochemistry.(Screening through 12 weeks post-final cycle.)
- Identification of peripheral patient selection and pharmacodynamic markers from blood samples that predict and/or correlate with response to treatment.(Screening through 12 weeks post-final cycle.)