A Phase 2 Study of Avutometinib (VS-6766, a Dual RAF/MEK Inhibitor) In Combination With Defactinib (FAK Inhibitor) in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) in Japanese Patients
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 16
- 试验地点
- 5
- 主要终点
- Confirmed overall response rate (ORR; partial response [PR] + complete response [CR]
研究概览
简要总结
This study will confirm the safety and efficacy of avutometinib in combination with defactinib in Japanese patients with recurrent Low-Grade Serous Ovarian Cancer (LGSOC)
详细描述
This is a multi-center, open label Phase 2 study designed to evaluate safety and tolerability and confirm efficacy by BICR of avutometinib in combination with defactinib in Japanese patients with molecularly profiled recurrent LGSOC.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically proven LGSOC (ovarian, peritoneal)
- •Documented mutational status of KRAS by validated diagnostic test of tumor tissue
- •Documented disease progression (radiographic or clinical) or recurrence of LGSOC and have received at least one platinum-based chemotherapy agent
- •Measurable disease according to RECIST 1.1
- •An Eastern Cooperative Group (ECOG) performance status ≤
- •Adequate organ function
- •Adequate recovery from toxicities related to prior treatments
- •Agreement to use highly effective method of contraceptive, if necessary
排除标准
- •Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
- •Co-existing high-grade ovarian cancer or another histology
- •History of prior malignancy, excluding ovarian cancer, with recurrence <3 years from the time of enrollment
- •Major surgery within 4 weeks
- •Symptomatic brain metastases requiring steroids or other interventions
- •Known SARS-Cov2 infection (clinical symptoms) ≤28 days prior to first dose of study therapy
- •For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor
- •Active skin disorder that has required systemic therapy within the past year
- •History of rhabdomyolysis
- •Concurrent ocular disorders
- •Concurrent heart disease or severe obstructive pulmonary disease
- •Patients with the inability to swallow oral medications
研究组 & 干预措施
avutometinib + defactinib
Avutometinib 3.2mg, PO, twice weekly for 21 days on, 7 days off in a 28-day (4 weeks) cycle in combination with defactinib 200 mg, PO, twice daily for 21 days on, 7 days off in a 28-day (4 week) cycle.
干预措施: Avutometinib (VS-6766) + Defactinib (VS-6063) (Drug)
结局指标
主要结局
Confirmed overall response rate (ORR; partial response [PR] + complete response [CR]
时间窗: From start of treatment to confirmation of response; 24 weeks
Confirmed overall response rate (ORR; partial response \[PR\] + complete response \[CR\] defined according to Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) as assessed by the blinded independent central radiology review committee (BICR)
次要结局
- Clinical benefit rate(6 months)
- Duration of Response(12 months)
- Objective response rate (ORR)(12 months)
- Progression free survival (PFS)(24 months)
- Disease control rate (DCR)(6 months)
- Overall Survival (OS)(up to 2 years)
- Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)(18 months)
- Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites(9 months)
- Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites(9 months)