An Open-Label, Multicenter, Phase 1 Study to Evaluate Safety, Pharmacokinetics, and Preliminary Anti-Tumor Activity of RO7515629 in Participants With Unresectable and/or Metastatic HLA-G Positive Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Part 1, 2, 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The main purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, immune response and preliminary anti-tumor activity of RO7515629 alone in participants with advanced or metastatic solid tumors expressing human leukocyte antigen G (HLA-G).
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
- •Unresectable and/or metastatic HLA-G-positive solid tumors, for which standard therapy does not exist, or has proven to be ineffective or intolerable
- •Confirmed HLA-G tumor expression.
- •Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Life expectancy of at least 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate hematological, liver, renal and pulmonary function
- •Willingness to abide by protocol defined contraceptive requirements for the duration of the study.
排除标准
- •History or clinical evidence of Central Nervous System (CNS) metastases unless protocol specified criteria are met
- •Leptomeningeal metastases
- •Rapid disease progression including lesions that are a threat to vital organs or non-irradiated lesions 2cm or larger at critical sites where tumor swelling may pose a risk to critical anatomical structures
- •Participants with another invasive malignancy in the last 2 years unless protocol specified criteria are met
- •Uncontrolled hypertension
- •Active interstitial lung disease (ILD), pneumonitis or a history of ILD/pneumonitis requiring treatment with steroids, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan
- •Participants with central cavitation or tumor(s) shown to be invading or abutting major blood vessels by imaging or the Investigator determines the tumor(s) is likely to invade major blood vessels and cause fatal bleeding
- •Participants with pulmonary military metastatic pattern or pulmonary lymphangitic carcinomatosis
- •History of pulmonary embolism within 3 months prior to study entry
- •Significant cardiovascular disease
- •Presence of active or uncontrolled infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to initiation of study treatment.
- •Known hepatitis B or C (actively replicating) based on protocol specified criteria
- •Known Human Immunodeficiency Virus (HIV) positivity
- •Presence of an indwelling line or drain
- •Active auto-immune disease that has required systemic therapy within the past 2 years unless protocol specified exceptions are met
- •Major surgery within 28 days prior to first study treatment
- •Last treatment with anti-cancer therapy or any investigational drug 28 days or less prior to the first study treatment
- •Last dose of immunostimulating or immunosuppressive therapy 28 days or less prior to the first study treatment
- •Regular dose of corticosteroids that exceeds prednisone 10 mg/day or equivalent within 28 days prior to first study treatment
- •Prior treatment with T cell engaging or adoptive cell therapy
- •Administration of a live, attenuated vaccine 28 days or less prior to first study treatment
- •Contraindication or known hypersensitivity to any of the components of RO7515629 or tocilizumab or dexamethasone
研究组 & 干预措施
Part I Single Participant Cohort RO7515629 Dose Escalation
Participants will receive a fixed dose of RO7515629 intravenously as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
干预措施: RO7515629 (Drug)
Part I Single Participant Cohort RO7515629 Dose Escalation
Participants will receive a fixed dose of RO7515629 intravenously as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
干预措施: tocilizumab (Drug)
Part II Multiple Participant Cohort RO7515629 Dose Escalation
Participants will receive RO7515629 intravenously, as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. In case of toxicity, step up dosing (single or double) may be implemented. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
干预措施: RO7515629 (Drug)
Part II Multiple Participant Cohort RO7515629 Dose Escalation
Participants will receive RO7515629 intravenously, as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. In case of toxicity, step up dosing (single or double) may be implemented. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
干预措施: tocilizumab (Drug)
Part III Multiple Participant Cohort RO7515629 Dose Expansion
Participants with selected solid tumors will receive a selected dose of RO7515629 intravenously as a single agent based on the recommended dose sequence for expansion (RDE) and dosing regimen selected from Part I and Part II. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
干预措施: RO7515629 (Drug)
Part III Multiple Participant Cohort RO7515629 Dose Expansion
Participants with selected solid tumors will receive a selected dose of RO7515629 intravenously as a single agent based on the recommended dose sequence for expansion (RDE) and dosing regimen selected from Part I and Part II. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
干预措施: tocilizumab (Drug)
结局指标
主要结局
Part 1, 2, 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 15 months
Part 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: From start of study treatment (cycle 0 day -7 or cycle 0 day -14) until two weeks after second or third RO7515629 infusion (cycle 1 day 1) for a total DLT window of up to 28 days.
次要结局
- Part 1, 2, 3: Pharmacokinetic Analysis: Maximum Serum Concentration (Cmax) of RO7515629(Up to 13 months)
- Parts 1, 2, 3: Pharmacokinetic Analysis: Clearance (CL) of RO7515629(Up to 13 months)
- Part 1, 2, 3: Pharmacokinetic Analysis: Area Under The Curve (AUC) of RO7515629(Up to 13 months)
- Part 1, 2, 3: Pharmacokinetic Analysis: Time of Maximum Serum Concentration (Tmax) of RO7515629(Up to 13 months)
- Part 1, 2, 3: Pharmacokinetic Analysis: Minimum Serum Concentration (Cmin) of RO7515629(Up to 13 months)
- Part 1, 2, 3: Pharmacokinetic Analysis: Volume of Distribution at Steady State (Vss) of RO7515629(Up to 13 months)
- Part 1, 2, 3: Number of Participants With RO7515629 Anti-drug Antibodies (ADAs)(Up to 13 months)
- Part 1, 2, 3: Disease Control Rate (DCR)(Up to approximately 18 months)
- Part 1, 2, 3: Duration of Response (DoR)(Up to approximately 18 months)
- Part 1, 2, 3: Objective Response Rate (ORR)(Up to approximately 18 months)
- Part 1, 2, 3: Overall survival (OS)(Up to approximately 18 months)
- Part 1, 2, 3: Progression Free Survival (PFS)(Up to approximately 18 months)