A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MOXR0916 and Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 610
- 试验地点
- 27
- 主要终点
- Number of Participants with Adverse Events Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.0
研究概览
简要总结
This Phase Ib, open-label, dose-escalation study will evaluate the safety, tolerability, and pharmacokinetics of the combination of MOXR0916 and atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy; or for which standard therapy has proven to be ineffective or intolerable or is considered inappropriate; or for which a clinical trial of an investigational agent is a recognized standard of care. Participants will be enrolled in two stages: a dose-escalation stage and an expansion stage.
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
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Life expectancy of at least 12 weeks
- •Adequate hematologic and end organ function
- •Histologic documentation of locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy; or for which standard therapy is ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is recognized standard of care
- •Tumor specimen availability
- •Measurable disease according to RECIST v1.1
排除标准
- •Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment
- •Malignancies other than disease under study within 5 years prior to D1 of C1
- •Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases
- •History of leptomeningeal disease
- •History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
- •History of autoimmune disease
- •Positive human immunodeficiency virus test result
- •Active hepatitis B, hepatitis C, or tuberculosis
- •Severe infection within 4 weeks prior to D1 of C1
- •Prior allogeneic bone marrow or solid organ transplantation
- •Significant cardiovascular disease
- •Known clinically significant liver disease
研究组 & 干预措施
Dose Escalation: MOXR0916 + Atezolizumab
Cohorts of at least 3 participants each will be treated at escalating doses of MOXR0916 in combination with a fixed dose of atezolizumab to determine the MTD or maximum administered dose (MAD).
干预措施: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody (Drug)
Dose Escalation: MOXR0916 + Atezolizumab
Cohorts of at least 3 participants each will be treated at escalating doses of MOXR0916 in combination with a fixed dose of atezolizumab to determine the MTD or maximum administered dose (MAD).
干预措施: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody (Drug)
Expansion: MOXR0916 + Atezolizumab
Approximately 250-580 participants will be enrolled in the expansion stage to better characterize the safety, tolerability, pharmacokinetic variability, biomarkers of anti-tumor activity, and preliminary efficacy of MOXR0916 + atezolizumab in different cancer types.
干预措施: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody (Drug)
Expansion: MOXR0916 + Atezolizumab
Approximately 250-580 participants will be enrolled in the expansion stage to better characterize the safety, tolerability, pharmacokinetic variability, biomarkers of anti-tumor activity, and preliminary efficacy of MOXR0916 + atezolizumab in different cancer types.
干预措施: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody (Drug)
结局指标
主要结局
Number of Participants with Adverse Events Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.0
时间窗: Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to 3 years)
Number of Participants with Dose-Limiting Toxicities (DLTs)
时间窗: Days (D) 1-21 of Cycle (C) 1 (cycle = 21 days); up to D42 if extended monitoring warranted
次要结局
- Maximum Tolerated Dose (MTD) of MOXR0916(Up to 1 year)
- Serum Maximum Observed Concentration (Cmax) of MOXR0916(Up to 120 days after the treatment discontinuation visit)
- Serum Cmin of Atezolizumab(Up to 120 days after the treatment discontinuation visit)
- Duration of Objective Response (DOR) Determined Using RECIST v1.1(From first objective response until death or relapse per RECIST v1.1, whichever occurs first (up to 3 years))
- Area under the Concentration-Time Curve (AUC) of MOXR0916(Up to 120 days after the treatment discontinuation visit)
- Percentage of Participants with Objective Response Determined Using Modified RECIST(Baseline until disease progression (up to 3 years))
- DOR Determined Using Modified RECIST(From first objective response until death or relapse per RECIST v1.1, whichever occurs first (up to 3 years))
- Overall Survival (OS)(Baseline until death (up to 3 years))
- Clearance (CL) of MOXR0916(Up to 120 days after the treatment discontinuation visit)
- Percentage of Participants with Objective Response Determined Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1(Baseline until disease progression (up to 3 years))
- PFS Determined Using Modified RECIST(Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years))
- Number of Cycles Received with MOXR0916(Baseline until treatment discontinuation (up to 3 years))
- Serum Cmax of Atezolizumab(Up to 120 days after the treatment discontinuation visit)
- Progression-Free Survival (PFS) Determined Using RECIST v1.1(Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years))
- Recommended Phase II Dose (RP2D) of MOXR0916(Up to 1 year)
- Percentage of Participants with Anti-MOXR0916 and Anti-Atezolizumab Antibodies(Up to 120 days after the treatment discontinuation visit)
- Dose Intensity of MOXR0916(Baseline until treatment discontinuation (up to 3 years))
- Serum Minimum Observed Concentration (Cmin) of MOXR0916(Up to 120 days after the treatment discontinuation visit)
- Volume of Distribution at Steady State (Vss) of MOXR0916(Up to 120 days after the treatment discontinuation visit)