A Multicenter, Dose-Escalation, Phase 1 Study of Samalizumab (ALXN6000) to Evaluate the Pharmacokinetics, Safety, and Tolerability in Patients With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 主要终点
- Maximum Plasma Concentration After Administration Of Samalizumab
研究概览
简要总结
This is a multicenter, open-label, dose-escalation, Phase 1 study of intravenous (IV) samalizumab to determine its maximum tolerated dose (MTD), overall safety/tolerability, pharmacokinetic and pharmacodynamic parameters, and efficacy in participants with advanced cancer. The study was terminated for administrative reasons and not due to any safety concerns.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Male or female participant was ≥ 18 years of age at Screening.
- •Eastern Cooperative Oncology Group performance status of 0 to
- •Participant had advanced/metastatic cancer with disease progression after treatment with all available therapies known to confer clinical benefit.
- •Participant had a life expectancy of greater than 12 weeks.
排除标准
- •Participant had a symptomatic brain metastasis.
- •Participant had active gastrointestinal bleeding as evidenced by either hematemesis or melena.
- •Participant had acute gastrointestinal ulcers.
- •Participant had a history of any cancer other than the present condition (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years.
- •Participant with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
- •Participant had an active infection requiring therapy.
- •Participant's serum was positive for the presence of hepatitis B surface antigen, antibodies to hepatitis C virus, or antibodies to human immunodeficiency virus 1/
- •Participant had significant cardiovascular impairment (history of New York Heart Association Functional Classification system Class III or IV) or a history of myocardial infarction or unstable angina within the past 6 months prior to study drug treatment.
- •The participant's most recent test values within 14 days before the date of entry met the following standards:
- •Bone marrow function: neutrophil count ≤1500/millimeter (mm)^3, hemoglobin ≤9.0 grams/deciliter, platelet count ≤100,000/mm^
- •Liver function: total bilirubin ≥1.5 x the upper limit of normal (ULN) based on the standard value of each institution, aspartate aminotransferase and alanine aminotransferase ≥2.5 x ULN based on the reference laboratory.
- •Renal function: serum creatinine ≥1.5 x ULN based on the reference laboratory.
- •Participant had ongoing immune-stimulated adverse events from other immunotherapies (for example, pneumonitis, thyroiditis, or hepatitis) or a history of pneumonitis.
- •Participant had received chemotherapy, targeted therapy, and/or immunotherapy within the 28 days prior to first dose of study drug, or within a Washout Period for the chemotherapy, targeted therapy, and/or immunotherapy of 5 half-lives, whichever occurred first.
- •Participant had toxicities from previous immunotherapy that had not resolved to Grade 1.
研究组 & 干预措施
Samalizumab 10, 15, 20 milligrams (mg)/kilogram (kg) Dose
Participants received escalating doses of 10, 15, and 20 mg/kg of samalizumab IV every 21 days. Enrollment at each dose level and safety assessments were completed prior to enrolling at the next dose level; intra-participant dose escalation was not allowed.
3 participants were enrolled into a dose cohort: If 0/3 participants developed dose limiting toxicities (DLT) within Cycle 1, enrollment began at the next higher dose to a maximum of 20 mg/kg. If 1/3 participants developed a DLT, the dose cohort was expanded to include 3 new participants. If 0/3 new participants developed a DLT within Cycle 1, enrolment began at the next higher dose level. If ≥1 of 3 new participants developed a DLT within Cycle 1, dose-escalation was terminated, and the dose level 5 mg/kg below the current dose was considered the MTD. If ≥2 of 3 participants developed DLTs within Cycle 1, dose-escalation was terminated, and the dose level 5 mg/kg below the current dose was considered the MTD.
干预措施: Samalizumab (Drug)
结局指标
主要结局
Maximum Plasma Concentration After Administration Of Samalizumab
时间窗: 21 days in Cycle 1
Number Of Participants Experiencing DLT Graded According To CTCAE Version 4.03, Observed In The Cycle 1 In Order To Meet The Objective Of Assessment Of The MTD
时间窗: Safety monitoring began at the informed consent obtained and continued up to 28 days after the last dose of samalizumab or until new anti-tumor therapy, whichever was earlier.
Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\]
Area Under The Plasma Drug Concentration-time Curve After Administration Of Samalizumab
时间窗: 21 days in Cycle 1
次要结局
- Objective Response Rate Using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1(Up to 2 Years)
- Progression Free Survival(Up to 2 Years)
- Overall Survival(Up to last participant completing at least 6 months)
- Disease Control Rate Using RECIST 1.1(Up to 2 Years)
- Duration Of Response(Up to 2 Years)