A Phase 1 Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of MSC-1 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 41
- 试验地点
- 7
- 主要终点
- Evaluate the safety and tolerability of MSC-1 and determine the recommended dose for MSC-1 monotherapy for further evaluation in the expansion part of the study
研究概览
简要总结
This is a 2-part study to evaluate the safety and antitumor activity of MSC-1. MSC-1 is a first-in-class, humanized monoclonal antibody (IgG1) which binds to the immunosuppressive human cytokine Leukemia Inhibitory Factor (LIF), and is intended to treat adult patients with Advanced Solid Tumors.
In part 1, multiple dose levels of MSC-1 in patients with advanced solid tumors will be studied to determine the recommended dose for further evaluation of safety and efficacy in Part 2.
详细描述
MSC-1 is a first-in-class, humanized monoclonal antibody (IgG1) which binds to the immunosuppressive human cytokine Leukemia Inhibitory Factor (LIF), and is intended to treat adult patients with advanced solid tumors. LIF is a pleiotropic cytokine involved in many physiological and pathological processes including the promotion of an immunosuppressive environment. In cancer, it is hypothesized that LIF expressing malignancies co-opt this activity, creating an immunosuppressive tumor microenvironment as well as promoting the activity of cancer-initiating cell(s) (CICs). LIF is highly expressed in a subset of tumors across multiple solid tumor types.
During dose escalation, patients with advanced solid tumors will be treated with MSC-1 with the primary objective of determining the safety and tolerability of MSC-1 and defining an appropriate dose for further evaluation in dose expansion. MSC-1 will be administered intravenously (IV) until disease progression, unmanageable toxicity, withdrawal of consent or study termination.
In dose expansion, up to 4 parallel cohorts of patients with LIF-High tumors (NSCLC, Ovarian Cancer, Pancreatic Cancer), and a cohort of mixed solid tumors (referred to as the "basket cohort"), may be treated at the recommended expansion dose to further characterize the safety, tolerability, PK, PD and anti-tumor activity of MSC-1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •(All patients):
- •Confirmed Advanced Unresectable Solid Tumor
- •Measurable disease by RECIST 1.1 by CT or MRI
- •Documented disease progression on or following last line of therapy
- •Archival tumor sample for submission
- •ECOG performance status 0 or 1
- •Resolution of all acute, reversible toxic effects of prior therapy or surgical procedures to at least grade 1 (except alopecia and peripheral neuropathy to at least grade 2)
- •Adequate organ function
- •A limited number of patients enrolled in Dose Escalation may be required to agree to pre- and on-treatment tumor biopsies
- •Inclusion Criteria (Dose Expansion patients only)
- •LIF- High NSCLC, Ovarian Cancer, or Pancreatic Cancer for the tumor-specific cohorts or Advanced Solid Tumor for the basket cohort as assessed by tumor tissue evaluation by IHC
- •All patients enrolled in Dose Expansion must agree to undergo pre- and on-treatment tumor biopsies
排除标准
- •(All Patients):
- •Systemic anti-cancer therapy within 4 weeks or 5 half-lives prior to study entry
- •Previous or concurrent malignancy that could affect compliance with protocol or interpretation of results
- •Clinically significant, unstable cardiovascular or pulmonary disease as specified in detail in the study protocol
- •History of acquired or congenital immunodeficiency syndrome or receiving immunosuppressive therapy
- •Uncontrolled infections or serologically positive HIV or hepatitis B or C infection
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase risk associated with study participation or interfere with interpretation of study results
研究组 & 干预措施
Dose Escalation
Multiple dose levels of MSC-1 treatment once every 3 weeks
干预措施: MSC-1 (Biological)
Dose Expansion
MSC-1 treatment at the recommended Phase 2 dose once every 3 weeks
干预措施: MSC-1 (Biological)
结局指标
主要结局
Evaluate the safety and tolerability of MSC-1 and determine the recommended dose for MSC-1 monotherapy for further evaluation in the expansion part of the study
时间窗: Patients will be evaluated for approximately 6 months or until disease progression
Assessment of frequency \& severity of adverse events
Assess the preliminary anti-tumor activity of MSC-1 monotherapy
时间窗: Patients will be evaluated for approximately 6 months or until disease progression
Determine objective response rate (ORR)
次要结局
- Characterize the PK of MSC-1(Patients will be evaluated before and after each dose of MSC-1 for approximately 6 months or until disease progression. PK will be evaluated more frequently for the first 2 cycles of treatment)
- Confirm safest dose of MSC-1 for further study(Patients will be evaluated for approximately 6 months or until disease progression)