NCT02221960已完成1 期
A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI6383 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 9
- 主要终点
- Safety
研究概览
简要总结
To evaluate MEDI6383 when given alone or together with MEDI4736 in adult subjects with recurrent or metastatic solid tumors.
详细描述
This is a Phase 1, multicenter, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and antitumor activity of MEDI6383 alone and in combination with MEDI4736 in adult subjects with recurrent or metastatic solid tumors.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects; age ≥ 18
- •Written informed consent must be obtained
- •Subjects must meet the following criteria:
- •Have recurrent or metastatic solid tumors
- •Must have received and have progressed, are refractory, or are intolerant to standard therapy appropriate for the specific tumor type. Subjects should not have received more than 5 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies
- •Subjects must have at least 1 lesion
- •Subjects must consent to provide archived tumor specimens and / or tumor biopsy for correlative biomarker studies.
- •Eastern Cooperative Oncology Group performance score of 0 or 1
- •In the opinion of the invesgator likely to complete ≥ 8 weeks of treatment.
- •Adequate organ function as determined by:
- •i. Absolute neutrophil count ≥ 1.5 x 109/L (1,500/mm3) ii.Platelet count ≥ 100 x 109/L (100,000/mm3) iii.Hemoglobin ≥ 9.0 g/dL within first 2 weeks prior to first dose of investigational product iv.Calculated creatinine clearance* (CrCl) or 24 hour urine CrCl > 50 mL/min v.Total bilirubin ≤ 1.5× ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ≤ 3× ULN vi.Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5× ULN vii.Serum Electrolytes within normal limits
- •Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of highly effective contraception from screening, and must agree to continue using such precautions for 90 days after the final dose of investigational product; 10) Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1 through 90 days after receipt of the final dose of investigational product
排除标准
- •Prior treatment with TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR) .
- •Subjects who have received prior therapy with regimens containing CTLA-4, PDL-1, or PD-1 antagonists are NOT permitted to enroll unless all of the following apply:
- •Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
- •All AEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or baseline prior to screening for this study.
- •Must not have experienced a ≥ Grade 3 AE or neurologic or ocular AE of any grade while receiving prior immunotherapy
- •History of severe allergic reactions to any unknown allergens or any components of the study drug formulations
- •Active or prior documented autoimmune disease within the past 2 years.
- •Untreated central nervous system metastatic disease l
- •Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study
- •Receipt of anticancer therapy within 28 days prior to the first dose of Investigational Product
- •Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
- •Unresolved toxicities from prior anticancer therapy
- •Systemic anticoagulation or daily aspirin dose exceeding 325 mg per day
- •Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI
- •History of primary immunodeficiency, solid organ transplantation, or tuberculosis
- •True positive test results for human immunodeficiency virus (HIV) or hepatitis B or C
- •Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational products )
- •Pregnant or breastfeeding women
- •Major surgery (as defined by the investigator) within 4 weeks prior to first dose of MEDI6383 or still recovering from prior surgery. Local surgery of isolated lesions for palliative intent is acceptable
- •Other invasive malignancy within 2 years
研究组 & 干预措施
Combination Arm
Experimental
MEDI6383 and MEDI4736
干预措施: MEDI6383 and MEDI4736 (Biological)
Monotherapy Arm
Experimental
MEDI6383
干预措施: MEDI6383 (Biological)
结局指标
主要结局
Safety
时间窗: From time of informed consent through 12 weeks after last dose of investigational product
Primary endpoint will be the number (%) of subjects with adverse events and serious adverse events.
次要结局
- Preliminary Antitumor Activity(Duration of Study)
- Pharmacokinetics of MEDI6383 or MEDI6383/MEDI4736(From time of informed consent through 12 weeks after last dose of investigational product)
- Biomarker Activity(From time of informed consent through 12 weeks after last dose of investigational product)
- Immunogenicity(From time of informed consent through 12 weeks after last dose of investigational product)
研究者
研究点 (9)
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