A Phase 1, Open-Label, Dose Escalation Study of MGA271 in Combination With Pembrolizumab and in Combination With MGA012 in Patients With Melanoma, Squamous Cell Cancer of the Head and Neck, Non-Small Cell Lung Cancer, Urothelial Cancer, and Other Cancers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 146
- 试验地点
- 20
- 主要终点
- Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab
研究概览
简要总结
The purpose of this study is to evaluate the safety of enoblituzumab (MGA271) in combination with Keytruda (pembrolizumab) when given to patients with B7-H3-expressing melanoma, squamous cell carcinoma of the head and neck (SCCHN), non small cell lung cancer (NSCLC), Urothelial Cancer and other B7-H3 expressing cancers. The study will also evaluate what is the highest dose of enoblituzumab that can be given safely when given with pembrolizumab. Assessments will also be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics) and to evaluate potential anti-tumor activity of MGA271 in combination with pembrolizumab. Safety and efficacy of enoblituzumab in combination with MGA012 (anti-PD-1 monoclonal antibody; also known as INCMGA00012) will also be evaluated.
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
- •To enroll on cohorts 1-4, participants must have a histologically-proven, previously treated, unresectable, locally advanced or metastatic mesothelioma, urothelial cancer, thyroid cancer, pancreatic cancer, ovarian cancer, colon cancer, prostate cancer, soft tissue sarcoma, triple negative breast cancer, renal clear cell cancer, melanoma, squamous cell cancer of the head and neck, or non-small cell lung cancer.
- •Participants on the melanoma cohort must have progressed on or after at least one anti-PD-L1 or anti- PD-1 containing therapy.
- •Participants on the SCCHN cohort must have progressed on or after platinum-based systemic therapy
- •Participants on the NSCLC cohort must have progressed on or after first line systemic therapy
- •Participants on the urothelial cancer cohort must have received at least one platinum-containing regimen and have progressed on or after an anti-PD-L1 or anti-PD-1 containing therapy
- •Measurable disease per RECIST 1.1 criteria
- •Easter Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Acceptable laboratory parameters and adequate organ reserve.
排除标准
- •Patients with a history of symptomatic central nervous system metastases, unless treated and asymptomatic
- •Patients with history of autoimmune disease with certain exceptions such as vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic therapy within the past 2 years, patients with history of Grave's disease that are now euthyroid clinically and by lab testing
- •History of allogeneic bone marrow, stem cell, or solid organ transplant
- •Treatment with systemic cancer therapy or investigational therapy within 4 weeks of first study drug administration; radiation within 2 weeks; corticosteroids (greater than or equal to 10 mg prednisone or equivalent per day) or other immune suppressive drugs within 2 weeks of first study drug administration
- •Trauma or major surgery within 4 weeks of first study drug administration
- •History of clinically-significant cardiovascular disease; gastrointestinal perforation; gastrointestinal bleeding, acute pancreatitis or diverticulitis within 4 weeks of first study drug administration
- •Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days of first study drug administration
- •Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction (PCR)
- •Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome
- •Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the drug or vehicle formulation for MGA271 or pembrolizumab.
研究组 & 干预措施
Cohort 3
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Pembrolizumab (Biological)
Cohort 1
Enoblituzumab 3 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Enoblituzumab Schedule 1 (Biological)
Cohort 1
Enoblituzumab 3 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Pembrolizumab (Biological)
Cohort 2
Enoblituzumab 10 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Enoblituzumab Schedule 1 (Biological)
Cohort 2
Enoblituzumab 10 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Pembrolizumab (Biological)
Cohort 3
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Enoblituzumab Schedule 1 (Biological)
Cohort 4
Enoblituzumab 15 mg/kg IV plus retifanlimab 375 mg IV every 3 weeks
干预措施: Enoblituzumab Schedule 2 (Biological)
Cohort 4
Enoblituzumab 15 mg/kg IV plus retifanlimab 375 mg IV every 3 weeks
干预措施: retifanlimab (Biological)
Melanoma Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Enoblituzumab Schedule 1 (Biological)
Melanoma Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Pembrolizumab (Biological)
Urothelial Cancer Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Enoblituzumab Schedule 1 (Biological)
Urothelial Cancer Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Pembrolizumab (Biological)
Non-small Cell Cancer (NSCLC) Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Enoblituzumab Schedule 1 (Biological)
Non-small Cell Cancer (NSCLC) Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Pembrolizumab (Biological)
Squamous Cell Cancer of Head and Neck (SCCHN) Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Enoblituzumab Schedule 1 (Biological)
Squamous Cell Cancer of Head and Neck (SCCHN) Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab
时间窗: Study Day 1-42, for Cohorts 1-4.
Dose-limiting toxicities are severe side effects related to study treatment that may cause dose interruptions, dose reductions, or withdrawal of treatment.
次要结局
- ORR Using Immune-related (ir) RECIST Criteria(Six weeks after the first dose, then every 9 weeks throughout study until discontinuation, average 13 months)
- Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1(Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average13 months.)
- Mean Maximum Concentration of Enoblituzumab(Baseline, 1, 4, 24, and 72 hours after the first dose.)
- Mean Trough Concentration of Enoblituzumab(At baseline, and Day 7.)
- Mean Area Under the Concentration Time Curve (AUC) From Time 0 to Day 7 of Enoblituzumab(At baseline, 1, 4, 24, 72 hours, and Day 7.)
- Mean Clearance of Enoblituzumab(At baseline, 1, 4, 24, 72 hours, and Day 7.)
- Mean Volume of Distribution at Steady State of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab(At baseline, 1, 4, 24, and 72 and Day 7.)
- Best Overall Response (RECIST 1.1)(Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.)
- Median Progression-free Survival (PFS) Using RECIST 1.1(Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.)
- Mean Terminal Half-life of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab(At baseline, 1, 4, 24, and 72 and Day 7.)
- Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA)(Every 3 weeks throughout the study, average duration 13 months.)
- Number of Participants That Develop Retifanlimab ADA(Every 3 weeks throughout the study, average duration 13 months.)
- Minimum and Maximum DoR Per RECIST 1.1(Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.)
- Median PFS Using irRECIST 1.1 Criteria(Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.)
- Objective Response Rate(Six weeks after the first dose, then every 9 weeks throughout study until discontinuation, average 13 months)
- Best Overall Response (irRECIST 1.1)(Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.)
- Median Overall Survival(Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.)