An Open-label, Single-arm, Phase II Study of Regorafenib and Nivolumab in Patients With Mismatch Repair-Proficient (pMMR)/Microsatellite Stable (MSS) Colorectal Cancer (CRC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 70
- 试验地点
- 15
- 主要终点
- Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 Assessed by Investigator
研究概览
简要总结
The purpose of this study is to learn if combination of the two drugs regorafenib and nivolumab is an effective treatment for pMMR - MSS colorectal cancer, a special type of cancer of the colon or rectum (pMMR stands for proficient Mismatch Repair; MSS stands for Microsatellite Stable) and whether it is safe for patients. Regorafenib works by blocking several different proteins involved in tumor growth. Nivolumab is an immunotherapy drug encouraging the body's own immune system to attack cancer cells.
Both drugs have been approved, but not for how they are being used as combination therapy in this study. Brand name of regorafenib is Stivarga; brand name of nivolumab is Opdivo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Histological or cytological confirmed advanced, metastatic, or progressive pMMR/MSS adenocarcinoma of colon or rectum
- •Participant must have progressed or be intolerant to prior systemic chemotherapy including fluoropyrimidines, irinotecan, oxaliplatin, anti-vascular endothelial growth factor (VEGF) therapy, and, if extended rat sarcoma viral oncogene homolog (RAS) wild type, an anti-epidermal growth factor receptor (EGFR) therapy. Exceptions may apply
- •Participants must have adequate organ and marrow function defined by protocol-specified laboratory tests
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Measurable disease as determined by response evaluation criteria in solid tumors (RECIST) v1.1
- •Provision of recently obtained tumor tissue as per protocol specified requirement
- •Anticipated life expectancy greater than 3 months
- •Be able to swallow and absorb oral tablets
排除标准
- •Participants with Mismatch repair deficient (dMMR) / microsatellite instable-high (MSI-H) colorectal cancer
- •Prior therapy with regorafenib, anti-programmed cell death protein 1 (PD-1), programmed cell death protein 1 ligand 1 (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of immunotherapy to treat cancer
- •Presence of active central nervous system (CNS) metastases; participants with stable CNS disease or previously treated lesions are eligible for study entry
- •Poorly controlled hypertension, defined as a blood pressure consistently above 150/90 mmHg despite optimal medical management
- •Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 6 months before the start of study medication. Active pulmonary emboli or deep vein thrombosis that are significant or not adequately controlled on anticoagulation regimen
- •Any hemorrhage or bleeding event ≥ National Cancer Institute - Common terminology criteria for adverse events (NCI-CTCAE) Grade 3 within 28 days prior to the start of study medication
- •Participants with an active, known or suspected autoimmune disease
- •History of interstitial lung disease or pneumonitis
- •Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Regorafenib + Nivolumab
干预措施: Regorafenib (Stivarga, BAY73-4506) (Drug)
Regorafenib + Nivolumab
干预措施: Nivolumab (Opdivo) (Biological)
结局指标
主要结局
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 Assessed by Investigator
时间窗: Through database cut-off date of 11-NOV-2020 (Primary Completion Date) (up to 13 months)
ORR was defined as the percentage of participants with overall response of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have decreased in size to have a short axis of \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
次要结局
- Disease Control Rate (DCR) at 8 and 16 Weeks(At 8, 16, 24, 32 and 40 weeks)
- Overall Survival (OS)(Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months))
- Duration of Response (DOR)(Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months))
- Progression-free Survival (PFS)(Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5(30 days after last dose of regorafenib and 100 days after last dose of nivolumab until study completion (up to 30 months))