An Open-label, Single-arm, Phase Ib/IIa Trial to Evaluate the Safety and Efficacy of the EP4 Receptor Antagonist Vorbipiprant (CR6086) in Combination With the PD-1 Inhibitor Balstilimab (AGEN2034), in Patients With Pretreated Mismatch-repair-proficient and Microsatellite Stable Metastatic Colorectal Cancer, and Other Metastatic GI Cancers.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 107
- 试验地点
- 3
- 主要终点
- Safety and Tolerability of CR6086 combined with AGEN2034
研究概览
简要总结
This Phase Ib/IIa study comprises a Main Study and a Study Extension.
The Main Study has been designed according to a 3+3 Dose Escalation/dose Expansion design in refractory pMMR-MSS mCRC patients. The fixed-dose Expansion phase will be conducted at the recommended dose for expansion (RDE), with the purpose of generating additional and more robust safety and efficacy data. 27 patients are predicted in the Dose Escalation phase and 52 in the Expansion phase, respectively.
The Study Extension explores in other metastatic GI cancers the Vorbipiprant (CR6086) RDE obtained in the Main Study. 27 patients are predicted.
No control arm was included, as the target patient population of this study consists of patients in whom the overall survival is less than 6 months and treatment options are very limited and often poorly tolerated, making unlikely that the study results can be significantly biased.
详细描述
In this study, the combination of the PGE2 inhibition (through the EP4 receptor antagonist CR6086) with the immune checkpoint blockade (through the anti-PD-1 AGEN2034) is being evaluated in refractory pMMR-MSS mCRC and other metastatic GI cancers. CR6086 (Vorbipiprant) is a potent and selective, orally bioavailable, targeted immunomodulator small molecule acting as an EP4 receptor antagonist. AGEN2034 (balstilimab) is a novel, fully human monoclonal immunoglobulin G4 antibody, designed to block programmed cell death 1 (PD-1) from interacting with its ligands (PD-L) PD-L1 and PD-L2, currently being developed for the treatment of advanced malignancies. EP4 receptor antagonists turn the status of the tumor microenvironment into a favourable one, i.e. immune-responsive, representing thus a rational therapeutic approach in combination with ICIs in primarily refractory cancers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
30 mg (Dose Level 1)
14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 30 mg twice a day for 14 days
干预措施: CR6086 (Drug)
30 mg (Dose Level 1)
14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 30 mg twice a day for 14 days
干预措施: AGEN2034 (Biological)
90 mg (Dose Level 2)
14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days
干预措施: CR6086 (Drug)
90 mg (Dose Level 2)
14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days
干预措施: AGEN2034 (Biological)
180 mg (Dose Level 3)
14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 180 mg twice a day for 14 days
干预措施: CR6086 (Drug)
180 mg (Dose Level 3)
14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 180 mg twice a day for 14 days
干预措施: AGEN2034 (Biological)
other mGI cancers
14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days
干预措施: CR6086 (Drug)
other mGI cancers
14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days
干预措施: AGEN2034 (Biological)
Expansion in MSS/pMMR mCRC patients
14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days
干预措施: CR6086 (Drug)
Expansion in MSS/pMMR mCRC patients
14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days
干预措施: AGEN2034 (Biological)
结局指标
主要结局
Safety and Tolerability of CR6086 combined with AGEN2034
时间窗: From the time of the first dose up to 24 weeks of treatment
Incidence of TEAEs using NCI CTCAE v5.0
Disease Control rate (DCR)
时间窗: up to 24 weeks of treatment
Proportion of patients who have achieved CR, PR, or stable disease (SD) per RECIST 1.1 / iRECIST during the Dose Escalation part
Objective Response Rate (ORR)
时间窗: up to 24 weeks of treatment
Proportion of patients who have achieved CR or PR per RECIST 1.1 / iRECIST during the Expansion part (Phase IIa)
次要结局
- Disease Control Rate (DCR)(throughout the study)
- Objective Response Rate (ORR)(throughout the study)
- Duration Of Response (DOR)(throughout the study, up to 2 years)
- Progression-Free Survival (PFR)(throughout the study, up to 2 years)
- Progression-Free Survival Rate (PFSR)(throughout the study, up to 2 years)
- Overall Survival (OS)(throughout the study, up to 2 years)
- Safety and Tolerability of CR6086 combined with AGEN2034(throughout the study, up to 2 years)