A Phase I/Ib Study to Evaluate the Safety, Tolerability, Biological and Clinical Activities of GEN-001 in Combination With Avelumab in Patients With Advanced Solid Tumors Who Have Progressed During or After Treatment With Anti-PD-(L)1 Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 11
- 试验地点
- 3
- 主要终点
- Dose Escalation: Incidence of Adverse Events
研究概览
简要总结
This is a phase I/Ib, first-in-human (FIH), open-label, dose escalation and dose expansion study to evaluate the safety and tolerability, biological and clinical activities of GEN-001 in patients with locally advanced or metastatic solid tumors who have progressed on at least two lines of approved therapy for their histological subtypes which includes an anti-PD-1 or anti-PD-L1 based therapy (as mono or combination), when administered as combined with avelumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Have adequate organ functions as defined in the protocol
- •Negative childbearing potential
- •Have ability to swallow and retain oral medication and no clinically significant gastrointestinal abnormalities
- •Patients with diseases for which no curative therapies are available, and who have progressed on at least two lines of approved therapy for their histological subtypes which includes an anti-PD-1 or anti-PD-L1 based therapy (as mono or combination)
- •Disease progression on anti-PD-(L)1 based therapy (as monotherapy or combination therapy) and must meet criteria for acquired resistance as defined in the protocol
- •Patients who have completely recovered from any clinically significant AEs that occurred during prior immunotherapy
- •Estimated life expectancy of at least 3 months
- •Objective evidence of disease progression at baseline (Dose Escalation)
- •Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic NSCLC, SCCHN, and UC (Dose Expansion)
- •Measurable disease as per RECIST v1.1 defined as at least 1 lesion (Dose Expansion)
排除标准
- •Have experienced primary resistance to anti-PD-(L)1 based therapy
- •Has experienced a toxicity that led to permanent discontinuation of prior anti-PD-(L)1 based therapy or other immunotherapies
- •Has active autoimmune disease that has required systemic treatment in the past 2 years
- •Current use of immunosuppressive medication at time of study entry
- •Have an active infection requiring antibiotics, antifungal or antiviral agents or have received a course of antibiotics within the previous 4 weeks of starting study treatment
- •Has received a live vaccine within 4 weeks of starting of study treatment
- •Known history of, or any evidence of active, non-infectious pneumonitis
- •Prior solid organ or allogeneic stem cell transplantation
- •Has had any investigational or anti-tumor treatment within 4 weeks or 5 half-life periods of starting study treatment, had any major surgeries within 4 weeks of starting study treatment
- •Has received proton pump inhibitors (PPIs) within 2 weeks prior to dosing study treatments
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has clinically significant (i.e., active) cardiovascular disease
- •Has known history of uncontrolled intercurrent illness
- •Has any psychiatric condition that would prohibit the understanding or rendering of informed consent or that would limit compliance with study requirements.
研究组 & 干预措施
GEN-001 with avelumab
Dose Escalation Cohort includes patients with advanced or metastatic solid tumors who have progressed on at least two lines of approved therapy for their histological subtypes which includes an anti-PD-1 or anti-PD-L1 based therapy (as mono or combination) will be enrolled. 3 or 6 patients will be enrolled per escalating or de-escalating dose levels.
Dose Expansion Cohort includes patients with advanced or metastatic NSCLC, SCCHN, and UC who have progressed on at least two lines of approved therapy for their histological subtypes which includes an anti-PD-1 or anti-PD-L1 based therapy (as mono or combination)will be enrolled.
干预措施: GEN-001 (Drug)
GEN-001 with avelumab
Dose Escalation Cohort includes patients with advanced or metastatic solid tumors who have progressed on at least two lines of approved therapy for their histological subtypes which includes an anti-PD-1 or anti-PD-L1 based therapy (as mono or combination) will be enrolled. 3 or 6 patients will be enrolled per escalating or de-escalating dose levels.
Dose Expansion Cohort includes patients with advanced or metastatic NSCLC, SCCHN, and UC who have progressed on at least two lines of approved therapy for their histological subtypes which includes an anti-PD-1 or anti-PD-L1 based therapy (as mono or combination)will be enrolled.
干预措施: Avelumab (Drug)
结局指标
主要结局
Dose Escalation: Incidence of Adverse Events
时间窗: 1 years
Assessed as per CTCAE v5.0
Dose Escalation: Incidence of Laboratory abnormalities
时间窗: 1 years
Assessed as per CTCAE v5.0
Dose Escalation: Incidence of dose-limiting toxicity (DLT)
时间窗: 1 Cycle (one cycle = 28 days)
To evaluate the safety and tolerability of GEN-001 in combination with avelumab
Dose Expansion: To assess objective response (OR) of GEN-001 in patients with advanced or metastatic solid tumors, when administered as combined with avelumab.
时间窗: 2 years
Confirmed OR per RECIST v1.1 by the Investigator
次要结局
- Objective Response (OR)(1 years)
- Progression-free survival (PFS)(up to 2 years)
- Incidence of Adverse Events(up to 2 years)
- Incidence of Laboratory Abnormalities(up to 2 years)
- irOR (Immune-related Objective Response)(up to 2 years)
- Duration of response (DoR)(up to 2 years)
- Overall Survival (OS)(up to 2 years)