An Open-label, Multicenter, Phase I Study to Evaluate Safety, Pharmacokinetics, and Preliminary Anti-tumor Activity of RO7444973 in Participants With Unresectable and/or Metastatic MAGE-A4-positive Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 10
- 主要终点
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is a first-in-human, open-label, uncontrolled, multi-center, monotherapy dose-escalation and dose expansion study of RO7444973.The aim of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of RO7444973 in participants with unresectable and/or metastatic melanoma-associated antigen A4 (MAGE-A4)-positive, solid tumors, carrying the HLA-A*02:01 allele.
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
- •Unresectable and/or metastatic solid tumors that have received standard-of-care (SOC) therapies previously and have no other SOC options available
- •Confirmed HLA-A*02:01 haplotype
- •Confirmed MAGE-A4 expression
- •Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Life expectancy of >/=12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Absence of rapid disease progression, threat to vital organs or non-irradiated lesions >2 cm in diameter at critical sites
- •No significant ongoing toxicity from prior anticancer treatment
- •Adequate hematological function
- •Adequate liver function
- •Adequate renal function
- •If applicable, willingness to use contraceptive measures.
排除标准
- •History or clinical evidence of CNS primary tumors or metastases
- •Another invasive malignancy in the last 2 years
- •Uncontrolled hypertension
- •Significant cardiovascular disease
- •Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic or other infection
- •Current or past history of CNS disease
- •Dementia or altered mental status that would prohibit informed consent
- •Active auto-immune disease or flare within 6 months prior to start of study treatment
- •Expected need for regular immunosuppressive therapy or with systemic corticosteroids
- •Insufficient washout from prior anti-cancer therapy
- •Prior treatment with a bispecific T-cell engaging or adoptive cell therapy.
研究组 & 干预措施
Part III: Recommended Phase 2 Dose (RP2D) Expansion
Based on emerging data from Part II, an RP2D and dosing regimen will be further investigated in Part III.
干预措施: RO7444973 (Drug)
Part I: Single Participant Cohort (SPC) Dose Escalation
In Part I, RO7444973 is administered intravenously (IV) every 3 weeks (Q3W) at a fixed dose in a single participant per dose level.
干预措施: RO7444973 (Drug)
Part I: Single Participant Cohort (SPC) Dose Escalation
In Part I, RO7444973 is administered intravenously (IV) every 3 weeks (Q3W) at a fixed dose in a single participant per dose level.
干预措施: Tocilizumab (Drug)
Part II: Multiple Participant Cohort (MPC) Dose Escalation
In Part II, RO7444973 is administered IV Q3W at a fixed dose in multiple participants per dose level. Step-up dosing may also be explored.
干预措施: RO7444973 (Drug)
Part II: Multiple Participant Cohort (MPC) Dose Escalation
In Part II, RO7444973 is administered IV Q3W at a fixed dose in multiple participants per dose level. Step-up dosing may also be explored.
干预措施: Tocilizumab (Drug)
Part III: Recommended Phase 2 Dose (RP2D) Expansion
Based on emerging data from Part II, an RP2D and dosing regimen will be further investigated in Part III.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From start of treatment up to 90 days after last RO7444973 dose (up to 15 months)
Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: From start of treatment up to 21-28 days
次要结局
- Objective Response Rate (ORR)(From baseline up to 12 months)
- Disease Control Rate (DCR)(From baseline up to 12 months)
- Duration of Response (DoR)(From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 40 months))
- Progression-free Survival (PFS)(From baseline to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 40 months))
- Overall Survival (OS)(From baseline to death from any cause (up to 40 months))
- Pharmacokinetics (PK): Serum Concentration of RO7444973 Over Time(From baseline to end of treatment (EoT) visit within 28 days after the last dose (up to 13 months))
- Change from Baseline in Percentage of Participants Positive for Anti-drug Antibodies (ADA) to RO7444973(From baseline to end of treatment (EoT) visit within 28 days after the last dose (up to 13 months))