A Phase Ia/Ib Open-label, Dose-escalation Study to Evaluate the Safety and Pharmacokinetics of ROSE12 as a Single Agent and in Combination With Other Anti-tumor Agents in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 209
- 试验地点
- 14
- 主要终点
- The area under the concentration time-curve (AUC) of ROSE12 for PK profile when administered as a single agent and in combination with atezolizumab (All Parts)
研究概览
简要总结
This is a Phase Ia/Ib open-label, dose-escalation study to evaluate the safety and pharmacokinetics of ROSE12 as a single agent and in combination with other anti-tumor agents in patients with locally advanced or metastatic solid tumors. The study will consist of three parts: a dose-escalation part, a biopsy part (the part to evaluate biomarkers), and an expansion part.
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
- •Age >= 18 years at time of signing informed consent form (ICF)
- •Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1
- •Adequate hematologic and end-organ function
- •Life expectancy >= 12 weeks
- •Patients with histologic documentation of locally advanced, or metastatic solid tumor
- •[Dose-escalation Parts and Biopsy Parts]Refractory or resistant to standard therapies or standard therapies are not available
- •[Dose-escalation Parts and Expansion Part] Patients with confirmed availability of fresh tumor or representative tumor specimens
- •[Biopsy Parts] Patients with accessible lesion(s)
- •[Expansion Parts] Patients with ICI (immune checkpoint inhibitor)-refractory 2L-3L NSCLC (non-small-cell lung cancer) and 3L+ CRC (colorectal cancer)
排除标准
- •Clinically significant cardiovascular or liver disease
- •Treatment with investigational therapy and anti-cancer therapy within 28 days prior to initiation of study drug
- •Any history of an immune-mediated Grade 4 adverse event attributed to prior cancer immunotherapy (other than asymptomatic elevation of serum amylase or lipase).
- •All imAEs from prior cancer immunotherapy (other than endocrinopathy managed with replacement therapy, stable vitiligo or stable alopecia) that have not resolved completely to baseline.
- •Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1 except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy
- •Primary central nervous system (CNS) malignancy, untreated CNS metastases requiring any anti-tumor treatment, or active CNS metastases
- •Uncontrolled tumor-related pain
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Active or history of clinically significant autoimmune disease
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
- •[Expansion Part]
- •Prior treatment with investigational product which has MoA of Treg depletion
- •Malignancies other than disease under study within 5 years prior to Cycle 1 Day 1
研究组 & 干预措施
Part C: Dose-escalation part of Phase Ib
Patients will receive ROSE12 and atezolizumab as a IV infusion at escalated doses.
干预措施: Atezolizumab (Drug)
Part D: Biopsy part of Phase Ib
Serial biopsy will be conducted with patients who will receive ROSE12 and atezolizumab as a IV infusion at escalated doses.
干预措施: Atezolizumab (Drug)
Part E: Expansion part of Phase Ib in patients with selected solid tumors
Patients will receive ROSE12 and atezolizumab as a IV infusion at the recommended dose.
干预措施: Atezolizumab (Drug)
Part D: Biopsy part of Phase Ib
Serial biopsy will be conducted with patients who will receive ROSE12 and atezolizumab as a IV infusion at escalated doses.
干预措施: ROSE12 (Drug)
Part B: Biopsy part of Phase Ia
Serial biopsy will be conducted with patients who will receive ROSE12 as a IV infusion at escalated doses.
干预措施: ROSE12 (Drug)
Part C: Dose-escalation part of Phase Ib
Patients will receive ROSE12 and atezolizumab as a IV infusion at escalated doses.
干预措施: ROSE12 (Drug)
Part A: Dose-escalation part of Phase Ia
Patients will receive ROSE12 as a IV infusion at escalated doses.
干预措施: ROSE12 (Drug)
Part E: Expansion part of Phase Ib in patients with selected solid tumors
Patients will receive ROSE12 and atezolizumab as a IV infusion at the recommended dose.
干预措施: ROSE12 (Drug)
结局指标
主要结局
The area under the concentration time-curve (AUC) of ROSE12 for PK profile when administered as a single agent and in combination with atezolizumab (All Parts)
时间窗: From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)
The area under the concentration time-curve (AUC) of ROSE12
Safety (All Parts) and tolerability (Part A, B, C and D) of ROSE12 when administered as a single agent and in combination with atezolizumab (Adverse Events)
时间窗: From screening until study completion, treatment discontinuation or post-treatment follow up, assessed up to the end of the study (approximate 43 months)
Incidence, nature, and severity of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
The maximum tolerated dose (MTD) and the recommended dose (RD) of ROSE12 when administered as a single agent and in combination with atezolizumab (Part A and C)
时间窗: From Cycle 1 Day 1 until Cycle 1 Day 21 (Cycle 1 is 21 days)
Incidence and nature of dose-limiting toxicities (DLTs)
The maximum serum concentration (Cmax) of ROSE12 for PK profile when administered as a single agent and in combination with atezolizumab (All Parts)
时间窗: From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)
The maximum serum concentration (Cmax) of ROSE12
The minimum serum concentration (Cmin) of ROSE12 for PK profile when administered as a single agent and in combination with atezolizumab (All Parts)
时间窗: From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)
The minimum serum concentration (Cmin) of ROSE12
Preliminary anti-tumor activity of ROSE12 when administered in combination with atezolizumab (Part E)
时间窗: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)
Objective response rate (ORR), defined as the proportion of patients with an objective response (complete response \[CR\] or partial response \[PR\]) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1
Safety (All Parts) and tolerability (Part A, B, C and D) of ROSE12 when administered as a single agent and in combination with atezolizumab or pembrolizumab (Adverse Events)
时间窗: From screening until study completion, treatment discontinuation or post-treatment follow up, assessed up to the end of the study (approximate 43 months)
Incidence, nature, and severity of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
The maximum serum concentration (Cmax) of ROSE12 for PK profile when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)
时间窗: From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)
The maximum serum concentration (Cmax) of ROSE12
The minimum serum concentration (Cmin) of ROSE12 for PK profile when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)
时间窗: From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)
The minimum serum concentration (Cmin) of ROSE12
The area under the concentration time-curve (AUC) of ROSE12 for PK profile when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)
时间窗: From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)
The area under the concentration time-curve (AUC) of ROSE12
Preliminary anti-tumor activity of ROSE12 when administered in combination with atezolizumab or pembrolizumab (Part E and F)
时间窗: From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months)
Objective response rate (ORR), defined as the proportion of patients with an objective response (complete response \[CR\] or partial response \[PR\]) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1
次要结局
- Preliminary anti-tumor activity of ROSE12 when administered as a single agent and in combination with atezolizumab (Part A, B, C and D)(From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months))
- The maximum serum concentration (Cmax) of atezolizumab for PK profile when administered in combination with ROSE12 (Part C, D and E)(From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months))
- The immunogenicity of ROSE12 when administered as a single agent and in combination with atezolizumab (All Parts)(From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months))
- The immunogenicity of atezolizumab when administered in combination with ROSE12 (Part C, D and E)(From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months))
- Preliminary anti-tumor activity of ROSE12 when administered as a single agent and in combination with atezolizumab (All Parts)(From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months))
- The minimum serum concentration (Cmin) of atezolizumab for PK profile when administered in combination with ROSE12 (Part C, D and E)(From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months))
- The area under the concentration-time curve (AUC) of atezolizumab for PK profile when administered in combination with ROSE12 (Part C, D and E)(From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months))
- Preliminary anti-tumor activity of ROSE12 when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)(From screening until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months))
- The maximum serum concentration (Cmax) of pembrolizumab for PK profile when administered in combination with ROSE12 (Part F)(From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 24 months))
- The minimum serum concentration (Cmin) of pembrolizumab for PK profile when administered in combination with ROSE12 (Part F)(From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 24 months))
- The area under the concentration-time curve (AUC) of pembrolizumab for PK profile when administered in combination with ROSE12 (Part F)(From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 24 months))
- The immunogenicity of ROSE12 when administered as a single agent and in combination with atezolizumab or pembrolizumab (All Parts)(From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months))
- The immunogenicity of pembrolizumab when administered in combination with ROSE12 (Part F)(From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation, assessed up to the end of the study (approximate 43 months))