A Phase IB/II Single-arm Study of M7824 (MSB0011359C) in Combination With Gemcitabine in Adults With Previously Treated Advanced Adenocarcinoma of the Pancreas
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment
研究概览
简要总结
Background:
Pancreas cancer ranks 4th in all cancer-related deaths in the United States (U.S.) Gemcitabine is a standard treatment for it. M7824 (MSB0011359C) blocks a pathway that prevents the immune system from effectively fighting cancer. The two drugs together might help people with pancreas cancer.
Objective:
To test if giving M7824 together with gemcitabine is safe and causes tumors to shrink.
Eligibility:
People ages 18 and older with pancreatic cancer already treated with standard therapies
Design:
Participants will be screened with:
Medical history
Physical exam
Scans in a machine that takes pictures of the body
Blood, urine, and heart tests
Some participants may have a tumor sample removed.
Participants will get M7824 by intravenous (IV) once every 2 weeks. They will continue until their disease gets worse or they have unacceptable side effects.
After the first dose, participants will also get gemcitabine by IV once weekly for 7 weeks. Then they will get it as follows for up to 6 months: Skip 1 week, get the drug once a week for 3 weeks, skip 1 week.
Before treatment on the first day of each cycle, participants will repeat screening tests. They will also have:
Optional tumor biopsies before and after 3 cycles of therapy
Questions about their well-being and function
Genetic testing of tissue and blood samples
Participants will have a follow-up visit 4-5 weeks after they stop therapy. This includes a physical exam, blood and urine tests, and maybe a scan. If their disease does not get worse, they will be invited for scans every 12 weeks.
详细描述
Background:
- M7824 (MSB0011359C) is an investigational agent in phase IB/II clinical development with dual activity against transforming growth factor beta (TGF)-beta signaling (TGF-beta ligand trap; extracellular domain of human TGF-beta receptor II) and immune checkpoint ligand inhibition (PD-L1 inhibition; avelumab, fully human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) directed against human PD-L1) with an acceptable toxicity profile and early signals of anti-cancer activity including in pancreas cancer.
- Gemcitabine (2 <=,2 <=-Difluorodeoxycytidine) is a standard-of-care nucleoside analogue in pancreas cancer with immunomodulatory mechanisms of actions in pancreas cancer patients.
- Preclinical studies in autochthonous and syngeneic murine models have shown that TGF-beta inhibition and PD-L1 inhibition cooperate with gemcitabine to achieve reduction of tumor growth and extension of survival induce anti-tumor immunity and reprogram the immune landscape.
Objectives:
- To determine the safety and tolerability of M7824 in combination with gemcitabine in subjects with metastatic or locally advanced pancreas cancer.
- To determine best overall response (BOR) rate according to Response Evaluation Criteria (Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in advanced pancreas cancer subjects.
Eligibility:
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1/ Arm 1-Gemcitabine + de-escalating dose of M7824 (MSB0011359C)
Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824
干预措施: M7824 (Drug)
1/ Arm 1-Gemcitabine + de-escalating dose of M7824 (MSB0011359C)
Gemcitabine (dose based on genetic testing results) + de-escalating dose of M7824
干预措施: Gemcitabine (Drug)
2/ Arm 2-Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C)
Gemcitabine (dose based on genetic testing results) + RP2D of M7824
干预措施: M7824 (Drug)
2/ Arm 2-Gemcitabine + Recommended Phase 2 Dose (RP2D) of M7824 (MSB0011359C)
Gemcitabine (dose based on genetic testing results) + RP2D of M7824
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Phase IB: Number and Severity of Grade 1-2 Adverse Events Possibly, Probably, or Definitely Related to Treatment
时间窗: 30 days after treatment
Safety and tolerability of M7824 in combination with gemcitabine was assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v5.0. Grade 1 is mild; asymptomatic or mild symptoms. Grade 2 is moderate; minimal non-invasive intervention indicated.
Duration of Treatment-related Adverse Events (AEs)
时间窗: Time to resolution of adverse events, which is the time recorded until it took for the adverse event to resolve to grade 1 or less (if there is a death, it is that time), approximately 12 months.
Duration of treatment-related AE's is defined as the time from the date treatment consent signed to end of treatment. Grade 1-4 adverse events observed in participants with pancreatic cancer assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe or medically significant. And Grade 4 is life-threatening.
Phase II: Number of Participants With a Best Overall Response (BOR)
时间窗: Every 8 weeks, up to 2 years
Changes in tumor size and occurrence of metastases was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 to determine the best overall response: Complete Response (CR), Partial Response (PR), and Stable Disease (SD), whichever is recorded first. Complete Response is disappearance of all lesions, Partial Response is at least a 30% decrease in the sum of diameters of target lesions, and Stable Disease is when the sum of all target lesions does not qualify for CR, PR, or Progressive Disease (PD), defined as the appearance of new lesions.
Phase IB: Number and Severity of Grade 3-5 Adverse Events Possibly, Probably, or Definitely Related to Treatment
时间窗: 30 days after treatment
Safety and tolerability of M7824 in combination with gemcitabine was assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v5.0. Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life-threatening consequences, and Grade 5 is death related to adverse event.
次要结局
- Percentage of Evaluable Participants Alive at 6 Months and 9 Months(At 6 and 9 months)
- Number of Participants With an Immune-related Best Overall Response (irBOR)(Every 6-12 weeks, up to 1 year)
- Percentage of Participants Who Have Not Progressed at 3 Months(3 months)
- Overall Median Survival(up to 1 year)
- Overall Progression Free Survival(up to 6 months)
研究者
Udo Rudloff, MD
Principal Investigator
National Cancer Institute (NCI)