A Phase 1/2, Open-Label, Single-Arm, Dose-Escalation and Dose-Expansion Study of the Safety, Tolerability, Pharmacokinetic, and Antitumor Activity of E-602 as a Single Agent and in Combination With Cemiplimab in Patients With Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 13
- 主要终点
- Number of Participants Who Experienced AEs or SAEs
研究概览
简要总结
This is a Phase 1/2, first-in-human, open-label, dose escalation and dose-expansion study of E-602, administered alone and in combination with cemiplimab.
详细描述
This study is being conducted to evaluate the safety, tolerability, PK, pharmacodynamics, and antitumor activity of E-602 in subjects with advanced cancers.
Phase 1 of the study consists of dose escalation cohorts of E-602 as a monotherapy and in combination with cemiplimab. Dose escalation will utilize a modified 3+3 design. Any Phase 1 cohort may be backfilled, up to a total of 15 subjects to obtain additional safety, PK, and pharmacodynamic data at a particular dose level. Phase 1 will treat subjects with melanoma, ovarian cancer, non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, breast cancer, gastric/esophagogastric junction (EGJ) cancer, head and neck cancer, or urothelial cancer. The safety and pharmacodynamic data will be evaluated to identify the maximum tolerated dose and recommended Phase 2 dose level for E-602 as monotherapy and in combination with cemiplimab.
Phase 2 consists of dose-expansion disease cohorts in subjects with 3 types of advanced tumors: melanoma, NSCLC, and a third type to be determined (ovarian, colorectal, pancreatic, breast, gastric/EGJ, head and neck, or urothelial) based on available data. Phase 2 includes cohorts of E-602 as monotherapy and E-602 in combination with cemiplimab. For each cohort in Phase 2, Simon's minimax 2-stage design will be used.
The study is seeking to enroll a total of up to 273 subjects (up to 87 in Phase 1 and up to 186 in Phase 2). Subjects will participate in the study for about 16 months.
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
- •Subjects with advanced or relapsed/refractory melanoma, ovarian cancer, NSCLC, colorectal cancer, pancreatic cancer, breast cancer, gastric/esophagogastric junction (EGJ) cancer, head and neck cancer, or urothelial cancer who have failed prior therapies.
- •a. Subjects with melanoma, NSCLC, head and neck cancer, urothelial cancer, or mMSI-H or dMMR colorectal cancer must have had prior anti-PD-(L)1 pathway therapy and been deemed resistant (had progression on therapy or within 3 months of discontinuation of therapy).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Subject has disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.
- •Adequate bone marrow, coagulation, renal function, and liver function as determined by laboratory tests
排除标准
- •For cohorts receiving E-602 and cemiplimab combination therapy:
- •Prior moderate or severe hypersensitivity to cemiplimab or its formulation
- •History of severe (≥ Grade 3) autoimmune complications or discontinuation due to toxicity following treatment with an anti-PD-(L)1 pathway therapy as a monotherapy, with the exception of asymptomatic Grade 3 elevations in lipase and/or amylase not associated with clinical manifestations of pancreatitis.
- •Subject has an active autoimmune disease. The following are not exclusionary: vitiligo, type 1 diabetes, autoimmune endocrinopathies that are stable on hormone replacement therapy, or psoriasis that does not require systemic treatment.
- •Previously received idelalisib.
- •History of age-related macular degeneration (AMD).
- •Recent surgery, treatment with another investigational agent, active infection, non-healing wound or uncontrolled bleeding/bleeding diathesis.
- •Received a vaccine or prior radiotherapy within 14 days prior to Cycle 1 Day
- •Prior history of interstitial lung disease that required steroids or ≥ Grade 2 immune-related pneumonitis or has current non-infectious pneumonitis or interstitial lung disease. Subject has a history of ≥Grade 3 radiation pneumonitis, or Grade 2 radiation pneumonitis that has been active within the last 6 months.
- •Untreated brain metastases.
- •A known primary malignancy that is progressing or has required active treatment within the past 3 years.
- •Subject is taking the equivalent of >10 mg/day oral prednisone or on systemic immunosuppressive therapy.
- •Subject has had an allogeneic tissue or organ transplantation.
- •History of thromboembolic event unless the event occurred > 6 months from Cycle 1 Day 1 and the subject is on anti-coagulation treatment.
研究组 & 干预措施
Dose Escalation - Monotherapy
Subjects will receive E-602 as monotherapy.
Planned monotherapy dose levels: 1 mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg.
干预措施: E-602 (Biological)
Dose Escalation - Combination
Subjects will receive E-602 in combination with cemiplimab.
E-602 dose(s): Will be initiated at dose level(s) that have previously completed dosing and DLT assessments as monotherapy.
Cemiplimab dose: 350 mg.
干预措施: E-602 (Biological)
Dose Escalation - Combination
Subjects will receive E-602 in combination with cemiplimab.
E-602 dose(s): Will be initiated at dose level(s) that have previously completed dosing and DLT assessments as monotherapy.
Cemiplimab dose: 350 mg.
干预措施: Cemiplimab (Biological)
Expansion - Monotherapy
Subjects will receive E-602 as monotherapy at the recommended Phase 2 dose determined in Phase 1.
干预措施: E-602 (Biological)
Expansion - Combination
Subjects will receive E-602 in combination with cemiplimab.
E-602 dose: Subjects will receive E-602 at the recommended Phase 2 dose determined in Phase 1 in combination with cemiplimab.
Cemiplimab dose: 350 mg.
干预措施: E-602 (Biological)
Expansion - Combination
Subjects will receive E-602 in combination with cemiplimab.
E-602 dose: Subjects will receive E-602 at the recommended Phase 2 dose determined in Phase 1 in combination with cemiplimab.
Cemiplimab dose: 350 mg.
干预措施: Cemiplimab (Biological)
结局指标
主要结局
Number of Participants Who Experienced AEs or SAEs
时间窗: 15 Months
Number of participants who experienced an adverse events (AEs) or a serious adverse event (SAE)
次要结局
未报告次要终点