EUCTR2017-003464-12-ES进行中（未招募）1 期
An Open-label Phase 1b/2 Study of Binimetinib Administered in Combination with Nivolumab or Nivolumab Plus Ipilimumab in Patients with Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer with RAS Mutation
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 75
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •Prescreening Inclusion Criteria:
- •1. Provide a signed and dated Prescreening ICF.
- •2. Male or female = 18 years of age at the time of signing the Screening ICF.
- •3. Measurable, histologically/cytologically confirmed mCRC.
- •4. Have willingness or ability to participate in the study.
- •5. Able to provide a sufficient amount (tumor block or minimum of 6 slides) of representative tumor specimen (primary or metastatic, archival or newly obtained) for central laboratory testing of RAS mutation status and MSS.
- •a. If a fresh tissue sample is provided, a blood sample is required.
- •6. Have received no more than 2 prior lines of therapy (maintenance therapy given in the metastatic setting will not be considered a separate regimen). Generally, treatments that are separated by an event of progression are considered different regimens.
- •7. No known contraindications to study treatment.
- •Screening Inclusion Criteria:
- •1. Patients must meet all Prescreening inclusion criteria.
- •2. Provide a personally signed and dated Screening ICF.
- •3. mCRC categorized as MSS by polymerase chain reaction (PCR) per local assay at any time prior to Screening or by the central laboratory.
- •4. RAS mutation per local assay at any time prior to Screening or by the central laboratory.
- •5. Have received at least 1 prior line of therapy and meets at least one of the following criteria:
- •a. were unable to tolerate the prior first-line regimen
- •b. experienced disease progression during or after prior first-line regimen for metastatic disease
- •c. progressed during or within 3 months of completing adjuvant chemotherapy
- •Note: Generally, treatments that are separated by an event of progression are considered different regimens.
- •6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- •7. Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks; if a female patient is of childbearing potential, she must agree to follow instructions for acceptable or highly effective method(s) of contraception for the duration of study treatment and for 5 months after the last dose of study treatment with nivolumab (i.e., 30 days [duration of ovulatory cycle] plus the time required for the investigational drug to undergo approximately 5 half-lives)
- •8. Non-sterile male patients who are sexually active with female partners of childbearing potential must agree to follow instructions for acceptable or highly effective method(s) of contraception for the duration of study treatment and for 7 months after the last dose of study treatment with nivolumab (i.e., 90 days [duration of sperm turnover] plus the time required for the investigational drug to undergo approximately 5 half-lives) (Section 5.3).
- •9. Adequate renal and bone marrow function as measured by the following Screening laboratory values:
- •a. White blood cells (WBC) = 2000/µL
- •b. Neutrophils = 1500/µL
- •c. Platelets = 100 ×103/µL
- •d. Hemoglobin = 9.0 g/dL
- •e. Serum creatinine = 1.5 × upper limit of normal (ULN) or calculated creatinine clearance > 50 mL/min (using the Cockcroft Gault formula)
- •10. Adequate hepatic function characterized by the following Screening laboratory values:
- •a. Serum total bilirubin = 1.5 × ULN and < 2 mg/dL Note: Patients who have a total bilirubin level > 1.5 × ULN will be allowed if their indirect bilirubin level is = 1.5 × ULN.
- •b. ALT and/or AST = 2.5 × ULN, or = 5 × ULN in presence of liver metastases
- •11. Adequate cardiac function as follows:
- •a. LVEF = 50% or above insti
排除标准
- •Prescreening Exclusion Criteria:
- •1. Prior treatment with any MEK inhibitor.
- •2. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- •3. Any untreated central nervous system (CNS) lesion. However, patients are eligible if: a) all known CNS lesions have been treated with radiotherapy or surgery, and b) patients remained without evidence of CNS disease progression = 4weeks after treatment, and c) patients must be off corticosteroid therapy for = 3 weeks.
- •4. Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- •5. Partial or complete bowel obstruction.
- •6. Impaired gastrointestinal function or disease that may significantly alter the absorption of binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption) or baseline diarrhea = Grade 1.
- •7. Known history of RVO.
- •8. Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy
- •9. Known history of Gilbert’s syndrome.
- •10. Severe uncontrolled medical illness.
- •11. Psychiatric illness inhibiting informed consent or protocol compliance.
- •12. Pregnant or breastfeeding females.
- •13. History of severe hypersensitivity reactions to mAbs.
- •14. History of allergy or intolerance (unacceptable AEs) to study drug components or polysorbate-80-containing infusions.
- •Screening Exclusion Criteria:
- •1. Patients must not meet any of the Prescreening exclusion criteria.
- •2. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to first day of study treatment:
- •a. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) and topical steroids are allowed. Patients who have received acute and/or low-dose systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea or chronic use of = 10 mg/day of prednisone or dose-equivalent corticosteroid) may be enrolled in the study after discussion with and approval by the Sponsor’s Medical Monitor.
- •3. Impaired gastrointestinal function or disease that may significantly alter the absorption of binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption) or baseline diarrhea = Grade 1.
- •4. History of thromboembolic or cerebrovascular events = 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli.
- •5. Uncontrolled hypertension defined as persistent systolic blood pressure = 150 mmHg or diastolic blood pressure = 100 mmHg despite current therapy.
- •6. Concurrent neuromuscular disorder that is associated with the potential of elevated CK (e.g., inflammatory myopathies, muscular dystrophy,
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