Phase II Study of the Anti-Mesothelin Immunotoxin LMB-100 Followed by Pembrolizumab in Malignant Mesothelioma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of Participants With an Objective Response (Partial Response + Complete Response)
研究概览
简要总结
Background:
Treatment outcomes for people with pleural or peritoneal mesothelioma are often poor. The drug LMB-100 can attack and kill cancer cells. The drug pembrolizumab helps the immune system fight cancer. Together, these drugs might help people with these cancers.
Objective:
To test if pembrolizumab given after LMB-100 shrinks tumors in people with pleural or peritoneal mesothelioma.
Eligibility:
People ages 18 and older with pleural or peritoneal mesothelioma that has not responded to platinum-based therapy
Design:
Participants will be screened with:
Tumor sample. Participants will have a biopsy if one is needed.
Medical history
Physical exam
Blood, heart, and urine tests
X-rays and scans: Participants will lie on a table. A machine will take pictures of the body.
Participants will receive LMB-100 by intravenous (IV) on days 1, 3, and 5 of two 21-day cycles. They will be observed for up to 2 hours after each infusion. They will receive drugs like Benadryl, Tylenol, and Zantac to help with side effects.
Starting with the 3rd cycle, participants will receive pembrolizumab by IV on day 1 of each 21-day cycle for up to 2 years.
Participants will have blood and urine tests, heart tests, and chest x-rays at least once per cycle. They will have scans every 6 weeks.
Participants may opt to provide tumor biopsies before starting the first cycle, after 2 cycles of LMB-100, and after 2 cycles of pembrolizumab.
Participants will a follow-up visit 4-6 weeks after their last drug dose of the study drug. This includes blood and heart tests and scans. They may then have scans every 6 weeks.
Participants will be contacted once a year for follow-up.
详细描述
Background:
- LMB-100, and a closely related immunotoxin, SS1P, also targeting mesothelin, have been studied in previous Phase 1 clinical studies for mesothelioma and pancreatic cancer.
- LMB-100 has demonstrated anti-tumor efficacy against several mesothelin expressing tumor models including mesothelioma patient-derived xenografts (PDX) models
- Programmed cell death protein 1 (PD-1) (encoded by the gene Pdcd1) is an Ig superfamily member related to cluster of differentiation 28 (CD28) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) that has been shown to negatively regulate antigen receptor signaling upon engagement of its ligands
- The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress immune control. The normal function of PD-1, expressed on the cell surface of activated T-cells under healthy conditions, is to down-modulate unwanted or excessive immune responses, including autoimmune reactions.
- In immune-competent mice bearing human mesothelin expressing tumors local administration of LMB-100 with CTLA-4 blockade eradicates murine tumors by promoting anti-cancer immunity.
- LMB-100 treatment increase cluster of differentiation 8 (CD8)+ T cell infiltration in murine lung adenocarcinoma tumors that express human mesothelin.
- Combination treatment with LMB-100 plus anti-PD1 results in greater anti-tumor efficacy in murine lung cancer model
- Pembrolizumab is an anti PD-1 antibody that has demonstrated responses of long duration in clinical trials and has generally been well-tolerated
- It is hypothesized that the anti-mesothelin immunotoxin LMB-100 followed by pembrolizumab will result in greater anti-tumor efficacy in patients with mesothelioma.
Objectives:
- To determine the objective response rate of sequential therapy with LMB-100 followed by pembrolizumab in subjects with pleural and peritoneal mesothelioma.
Eligibility:
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1/LMB- 100+pembrolizumab
LMB-100 administered in cycles 1 and 2 + pembrolizumab administered in subsequent cycles.
LMB-100 140mcg/kg Intravenous infusion (IVI), Days 1, 3, 5 in cycles 1, 2. Pembrolizumab 200mg IVI, every (Q) subsequent cycle on Day 1.
干预措施: LMB-100 (Drug)
1/LMB- 100+pembrolizumab
LMB-100 administered in cycles 1 and 2 + pembrolizumab administered in subsequent cycles.
LMB-100 140mcg/kg Intravenous infusion (IVI), Days 1, 3, 5 in cycles 1, 2. Pembrolizumab 200mg IVI, every (Q) subsequent cycle on Day 1.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Number of Participants With an Objective Response (Partial Response + Complete Response)
时间窗: Every 6 weeks until disease progression, an average of 3.1 months
Number of participants who received at least 1 cycle of study therapy and who had their disease reevaluated that experienced a partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST criteria. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
次要结局
- Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).(Date treatment consent signed to date off study, approximately 22 months and 29 days.)
- Progression Free Survival (PFS)(Time from start of treatment to time of progression (on or after pembrolizumab) or death, whichever occurs first, an average of 6.5 months)
- Overall Survival (OS)(Time between the first day of treatment to the day of death, an average of 17 months)
- Duration of Overall Response (DOR)(Time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, an average of 3.1 months)
- Percentage of Participants With an Overall Response(An average of 3.1 months.)
研究者
Raffit Hassan, M.D.
Principal Investigator
National Cancer Institute (NCI)