NCT03258398已完成2 期
A Phase 2, Open-Label, Randomized, Non-Comparative Study With Preliminary Dose Finding to Evaluate eFT508 Monotherapy or eFT508 in Combination With Avelumab in Subjects With Microsatellite Stable Relapsed or Refractory Colorectal Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 6
- 主要终点
- Part 1: Proportion of subjects with a dose limiting toxicity (DLT) during the first treatment cycle
研究概览
简要总结
This is a Phase 2, open-label, 2-part, multicenter study in subjects with MSS relapsed/refractory colorectal cancer. The primary objective of Part 1 is to evaluate the safety and tolerability of escalating doses of eFT508 in combination with a fixed dose of avelumab to determine the maximum tolerated dose (MTD) of eFT508 and to select a recommended dose for Part 2. The primary objective of Part 2 is to evaluate antitumor activity of eFT508 at the recommended dose in combination with avelumab or eFT508 monotherapy. Parts 1 and 2 will also evaluate pharmacokinetics (PK) and pharmacodynamics.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •ECOG performance status of 0, 1, or 2
- •Pathologically documented diagnosis of colorectal adenocarcinoma.
- •Progressed on or intolerant of at least 2 prior cancer therapy regimens administered for metastatic disease.
- •Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥3 weeks before the start of study therapy.
- •Part 2 only: Presence of radiographically measurable disease (defined as the presence of ≥1 lesion that measures ≥10 mm [≥15 mm for lymph nodes]). Measurable disease that was previously radiated is only permitted if progressing.
- •Agrees to undergo a pretreatment and a post-treatment biopsy.
- •Microsatellite stable disease determined by IHC and/or polymerase chain reaction (PCR).
- •Adequate bone marrow function
- •Adequate hepatic function
- •Adequate renal function
- •Normal coagulation profile
- •Negative antiviral serology
- •Female subjects of childbearing potential must not be pregnant or breastfeeding
- •Willingness to use protocol-recommended methods of contraception or to abstain from heterosexual intercourse from start of therapy until at lest 30 days after the last dose of study therapy
- •Life expectancy of ≥3 months.
排除标准
- •History of another malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin; in situ cervical or breast carcinoma; adequately treated, papillary, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission, or any other cancer that has been in complete remission for ≥2 years.
- •Known symptomatic brain metastases requiring ≥10 mg/day of prednisolone (or its equivalent).
- •Significant cardiovascular disease.
- •Significant screening ECG abnormalities.
- •Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
- •Known history of colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis.
- •Ongoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis.
- •Evidence of an ongoing systemic bacterial, fungal, or viral infection.
- •Any condition that may impact the subject's ability to swallow oral medications.
- •Major surgery within 4 weeks before the start of study therapy.
- •Prior solid organ or bone marrow progenitor cell transplantation.
- •Prior therapy with any known inhibitor of MNK-1 or MNK-
- •Prior therapy with any of the following: PD-1, PD-L1, CTLA4 antibody, or any other drug targeting T cell checkpoint pathways.
- •Prior high dose chemotherapy requiring stem cell rescue.
- •Intolerance to or prior severe (≥Grade 3) allergic or anaphylactic reaction to infused antibodies or infused therapeutic proteins.
- •Vaccination within 4 weeks of the first dose of avelumab and while on study.
- •Ongoing immunosuppressive therapy.
- •Use of a strong inhibitor or inducer of cytochrome P450 3A4 (CYP3A4) within 7 days prior to the start of study therapy or expected requirement for use of a strong CYP3A4 inhibitor or inducer during study therapy.
- •Previously received investigational product in a clinical trial within 30 days or within 5 elimination half lives (whichever is longer) prior to the start of study therapy, or is planning to take part in another clinical trial while participating in this study.
- •Has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results
研究组 & 干预措施
Part 1: eFT508 plus avelumab dose finding Arm
Experimental
subjects will receive eFT508 in combination with a fixed dose of avelumab
干预措施: eFT508 (Drug)
Part 1: eFT508 plus avelumab dose finding Arm
Experimental
subjects will receive eFT508 in combination with a fixed dose of avelumab
干预措施: Avelumab (Drug)
Part 2: eFT508 plus avelumab
Experimental
subjects will receive eFT508 in combination with a fixed dose of avelumab
干预措施: eFT508 (Drug)
Part 2: eFT508 plus avelumab
Experimental
subjects will receive eFT508 in combination with a fixed dose of avelumab
干预措施: Avelumab (Drug)
Part 2: eFT508 alone
Experimental
subjects will receive eFT508 alone
干预措施: eFT508 (Drug)
结局指标
主要结局
Part 1: Proportion of subjects with a dose limiting toxicity (DLT) during the first treatment cycle
时间窗: 28 days
Part 2: Overall Response Rate
时间窗: 8-16 weeks
the proportion of subjects whose best overall response is a complete or partial response
次要结局
未报告次要终点
研究者
研究点 (6)
Loading locations...
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