A Phase Ib/II, Open-label, Multi-center, Dose Escalation Study of MEK162 in Combination With Panitumumab in Adult Patients With Mutant RAS or Wild-type RAS Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 53
- 试验地点
- 3
- 主要终点
- Number of Participants With Dose-limiting Toxicities (DLT): Phase 1b
研究概览
简要总结
The primary purpose of the phase Ib is to estimate the MTD/RPD2 and of the phase II is to assess the anti-tumor activity of MEK162 in combination with panitumumab.
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
- Other
- 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
- •Metastatic colorectal cancer
- •Progression on or following standard therapy, or no standard therapy (phase Ib). Progression on or following at least 2-prior fluoropyrimidine-containing chemotherapy regimens (phase II)
- •Written documentation of mutant or wild-type RAS
- •Life expectancy ≥ 3 months
- •ECOG performance status ≤ 2
排除标准
- •Phase II arms 1 and 4 only: previous treatment with cetuximab, panitumumab, and/or other EGFR inhibitors
- •Previous treatment with MEK-inhibitors
- •History of severe infusion reactions to monoclonal antibodies.
- •Symptomatic or untreated leptomeningeal disease
- •Symptomatic brain metastasis
- •Current evidence of retinal disease; history of CSR, RVO or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO and history of keratitis.
- •Acute or chronic pancreatitis
- •Clinically significant cardiac disease
- •Not adequate hematologic, renal and hepatic function
研究组 & 干预措施
Phase Ib: Dose escalation
Phase Ib: Dose escalation.
干预措施: MEK162 (Drug)
Phase Ib: Dose escalation
Phase Ib: Dose escalation.
干预措施: Panitumumab (Drug)
Phase II: Patients with mutant RAS mCRC
Patients with mutant RAS mCRC who have not been pretreated with an EGFR inhibitor (EGFRi), including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy.
干预措施: MEK162 (Drug)
Phase II: Patients with mutant RAS mCRC
Patients with mutant RAS mCRC who have not been pretreated with an EGFR inhibitor (EGFRi), including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy.
干预措施: Panitumumab (Drug)
Phase II: Patients with acquired mutant RAS mCRC
Patients with acquired mutant RAS mCRC who have been pretreated with anti-EGFR monoclonal antibody therapy, but have not been pre-treated with EGFR tyrosine kinase inhibitor therapy.
干预措施: MEK162 (Drug)
Phase II: Patients with acquired mutant RAS mCRC
Patients with acquired mutant RAS mCRC who have been pretreated with anti-EGFR monoclonal antibody therapy, but have not been pre-treated with EGFR tyrosine kinase inhibitor therapy.
干预措施: Panitumumab (Drug)
Phase II: Patients with WT RAS mCRC (pretreated)
Patients with WT RAS mCRC who have been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy.
干预措施: MEK162 (Drug)
Phase II: Patients with WT RAS mCRC (pretreated)
Patients with WT RAS mCRC who have been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy.
干预措施: Panitumumab (Drug)
Phase II: Patients with WT RAS mCRC (not pretreated)
Patients with WT RAS mCRC who have not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy.
干预措施: MEK162 (Drug)
Phase II: Patients with WT RAS mCRC (not pretreated)
Patients with WT RAS mCRC who have not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy.
干预措施: Panitumumab (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicities (DLT): Phase 1b
时间窗: Within the first 28 days of treatment with binimetinib and panitumumab (Cycle 1)
DLT was defined as an adverse event or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment (Cycle 1) with binimetinib and panitumumab and met any of the specified criteria.
Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2
时间窗: From the start of the treatment until CR or PR (approximately up to 11 months)
ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to \<10 mm. PR: at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
次要结局
- Number of Participants With Electrocardiogram (ECG) Abnormalities(Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE)(Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months))
- Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment(From the date of randomization to the date of the first documented PD or death (approximately up to 11 months))
- Number of Participants With Clinically Significant Laboratory Abnormalities(Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months))
- Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment(From the first documented occurrence of response (PR or CR) until the date of the first documented PD or death due to the underlying cancer (approximately up to 11 months))
- Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment(From the start of the treatment until disease progression (approximately up to 11 months))
- Number of Participants With Vital Sign Abnormalities(Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months))
- Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 1b(From the start of the treatment until disease progression (approximately up to 11 months))
- Overall Survival (OS)(From the start of treatment to the date of death due to any cause (approximately up to 11 months))