A Phase 1, Open-Label Study to Evaluate the Safety and Tolerability of MEDI-565 in Adults With Gastrointestinal Adenocarcinomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Determine the maximum tolerable dose (MTD) or optimal biological dose (OBD) of MEDI-565 in subjects with gastrointestinal (GI) adenocarcinomas for which no standard or curative treatments are available.
研究概览
简要总结
To determine the maximum tolerated dose and/or optimum biologic dose of MEDI-565 in adult subjects and evaluate the safety profile in adult subjects with advanced gastrointestinal adenocarcinomas who have no available standard or curative treatments.
详细描述
This is a FTIH, dose-escalation and expansion Phase 1 study. The first part is a multicenter, open-label, single-arm, dose-escalation study of MEDI-565 to determine the MTD or OBD and evaluate the safety, tolerability, PK, IM, and antitumor activity of MEDI 565 in adult subjects who have GI adenocarcinomas for which no standard or curative treatments are available. The second part is a dose-expansion study at the MTD or OBD in subjects with selected tumor types.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Age ≥ 18 years of age at the time of screening
- •Adequate contraception from screening through end of trial
- •For the dose-escalation phase, subjects with GI adenocarcinomas with no available standard or curative treatments
- •Adequate hematological function
- •Adequate organ function
- •For subjects who had prior treatment with chemotherapy, biological therapy, radiotherapy, or had prior surgery: eligible for study entry if at least 30 days have passed since their treatment/surgery
- •Life expectancy of at least 3 months
- •Karnofsky performance status ≥ 70%
- •Body weight ≥ 45 kg
排除标准
- •Concurrent enrollment in another clinical study
- •Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals
- •Prior treatment with MEDI-565
- •History of allergy or reaction to any component of the MEDI-565 formulation
- •History of malignancy other than GI adenocarcinoma, within 5 years prior to study entry, with the exception of ductal carcinoma in situ of the breast, basal cell carcinoma of the skin or carcinoma in situ of the cervix successfully treated with curative therapy
- •Diagnosis of hepatocellular carcinoma
- •Clinical history of significant CNS pathology
- •Active bacterial infection or known bacteremia.
- •Vaccination within 2 weeks prior to initiation of MEDI-565
- •Infection with HIV-1 or HIV-2; chronic infection with hepatitis B or C
- •History of primary immunodeficiency
- •History of chronic autoimmune disease
- •Elective surgery planned during the study period through 30 days after discontinuation of MEDI-
- •Treatment with any chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment within 30 days prior to study entry and not recovered from treatment
- •Treatment with any investigational agent within 30 days prior to initiation of MEDI-565
- •Regular dose of systemic corticosteroids during the 30 days prior to initiation of MEDI-565 or anticipated need of corticosteroids exceeding prednisone 40 mg/day of prednisone or equivalent during the trial, or any other systemic immunosuppressive therapy within 30 days prior to study entry (some maintenance doses allowed)
- •Contraindication to any protocol-specified concomitant medications administered during this study
- •Pregnancy or lactation
- •Evidence of any uncontrolled systemic disease (other than GI adenocarcinoma)
- •Recent history of cardiac disease, including myocardial infarction, unstable angina pectoris or uncontrolled arrhythmia within 6 months, or evidence of severe congestive heart failure
- •A marked baseline prolongation of corrected QT interval interval
研究组 & 干预措施
MEDI-565 - Dose Escalation
Up to 15 dose-escalation cohorts will be enrolled
干预措施: MEDI-565 (Drug)
MEDI-565 Dose Expansion Arm 1
20 subjects with selected gastrointestinal tumor type will receive MEDI-565 at the maximum tolerated dose or optimum biologic dose
干预措施: MEDI-565 (Drug)
MEDI-565 Dose Expansion Arm 2
20 subjects with selected gastrointestinal tumor type will receive MEDI-565 at the maximum tolerated dose or optimum biologic dose
干预措施: MEDI-565 (Drug)
MEDI-565 Dose Expansion Arm 3
Subjects with selected gastrointestinal tumor type will receive MEDI-565 at the maximum tolerated dose or optimum biological dose
干预措施: MEDI-565 (Drug)
结局指标
主要结局
Determine the maximum tolerable dose (MTD) or optimal biological dose (OBD) of MEDI-565 in subjects with gastrointestinal (GI) adenocarcinomas for which no standard or curative treatments are available.
时间窗: MTD/OBD will be evaluated from the time of first administration of MEDI-565 through the first 28-day cycle
MTD/OBD will be determined based on Dose Limiting Toxicities that will be evaluated from the time of first administration of MEDI-565 through the first 28-day cycle
Evaluate the safety profile in adult subjects with advanced gastrointestinal (GI) adenocarcinomas who have no available standard or curative treatments.
时间窗: AEs and SAEs will be reported through 30 days after the last dose of MEDI 565
The number (percentage) of subjects with AEs and SAEs reported through 30 days after the last dose of MEDI 565 will be summarized for all subjects who received at least one dose of study drug (Safety Population).
次要结局
- Assess the safety and antitumor activity of MEDI-565 in the dose-expansion phase.(3 years)
- Pharmacokinetics of MEDI-565(3 years)
- Immunogenicity of MED-565(3 years)