A Phase 1b, Open-Label, Dose-escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activities of a RAF Dimer Inhibitor BGB-283 in Combination With MEK Inhibitor PD-0325901 in Patients With Advanced or Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 91
- 试验地点
- 12
- 主要终点
- Objective response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in participants with selected tumor types
研究概览
简要总结
This is a 2-part Phase 1b study of BGB-283 (lifirafenib) and PD-0325901 (mirdametinib) combination in participants with tumors.
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
- •Able to provide informed consent
- •Age 18 on day of signing informed consent form (ICF) or of the legal age of consent in the jurisdiction in which the study is taking place
- •Advanced or metastatic, unresectable tumors (other than patients with tumors of the brain or central nervous system) who have experienced disease progression
- •Part A: NSCLC, CRC, ovarian cancer, endometrial cancer, thyroid cancer, melanoma, pancreatic cancer, and other)
- •Part B: NRAS mutated solid tumors must have a known mutation status and a histologically or cytologically confirmed advanced or refractory solid tumor. Up to 40% Melanoma and Up to 20% CRC.
- •Must have archival tumor tissue or agree to tumor biopsy
- •Measurable disease per RECIST 1.1
- •Eastern Cooperative Oncology Group performance status of less than or equal to 1
- •Life expectancy is greater than 12 weeks of the signing of ICF.
- •Adequate organ function and no transfusion within 14 days of first dose.
- •Females are of non-child bearing potential or willing to use contraception.
- •Males vasectomized or agree to use contraception.
排除标准
- •Central Nervous System metastasis
- •Any retinal pathology considered to be a risk factor for central serous retinopathy
- •History of glaucoma
- •Active parathyroid disorder or history of malignancy associated hypercalcemia
- •Clinically significant cardiac disease within the past 6 months of signing ICF.
- •LVEF less than 50%
- •Abnormal QT interval at Screening
- •Severe uncontrolled systemic disease
- •Clinically significant active or known history of liver disease. (Hepatitis B and Hepatitis C)
- •Hemorrhage or bleeding event at NCI-CTCAE v5.0 Grade 3 or higher within 28 days of first dose.
- •history of or ongoing Von Willebrand disease and/or other past or present bleeding disorders
- •Increased serum calcium
- •Inability to swallow oral medications
- •Ongoing radiation therapy or radio-cytotoxic therapy within prior 4 weeks. No chemotherapy, immunotherapy, biologic therapy, hormonal, or molecular targeted therapy within prior 2 weeks
- •Concomitant systemic or glucocorticoid therapy within 2 weeks
- •Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose or anticipates need for major surgery while on study
- •Concomitant medicines that are strong CYP3A inhibitors
- •History of toxicity from another RAF, MEK, ERK inhibitor requiring discontinuation of treatment from these drugs
- •Underlying medical conditions in investigator's opinion to be unfavorable to be a part of the study
- •Has been administered a live vaccine within 4 weeks (28 days) of initiation of study treatment. NOTE: injectable seasonal vaccines for influenza and COVID-19 are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part A: Dose Escalation/Dose finding Dose Level Cohorts ranging in dose levels and dose regimens.
Combination doses of, Mirdametinib at once a day and lifirafenib at once a day And Mirdametinib at twice a day and lifirafenib at once a day
干预措施: Lifirafenib (Drug)
Part A: Dose Escalation/Dose finding Dose Level Cohorts ranging in dose levels and dose regimens.
Combination doses of, Mirdametinib at once a day and lifirafenib at once a day And Mirdametinib at twice a day and lifirafenib at once a day
干预措施: mirdametinib (Drug)
Part B: Expansion
Approximately 20 participants with NRAS mutated solid tumors will be enrolled
干预措施: Lifirafenib (Drug)
Part B: Expansion
Approximately 20 participants with NRAS mutated solid tumors will be enrolled
干预措施: mirdametinib (Drug)
结局指标
主要结局
Objective response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in participants with selected tumor types
时间窗: Approximately 2 years from date of the participants enrollment
The incidence of DLT events and treatment-emergent AEs (TEAEs)
时间窗: Approximately 2 years from date of the participants enrollment
Adverse Events and Serious Adverse Events
时间窗: Approximately 2 years from date of the participants enrollment
Incidence and severity of AEs and SAEs and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
次要结局
未报告次要终点