A Phase 2, Subprotocol of DAY101 Monotherapy for Patients With Recurrent, Progressive, or Refractory Solid Tumors With MAPK Pathway Aberrations
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 20
- 主要终点
- Overall Response Rate (ORR) by the Investigator
研究概览
简要总结
This is a Phase 2, multi-center, open-label to evaluate the efficacy and safety of tovorafenib (DAY101) in participants ≥12 years of age with recurrent or progressive melanoma or solid tumors with BRAF fusion or CRAF/RAF1 fusions or amplification.
详细描述
Study DAY101-102 (master study) and sub-studies will consist of a screening period, a treatment period, a safety follow-up period, and a long-term follow-up period where survival, status and subsequent anticancer therapies are collected.
Tovorafenib will be evaluated alone or combined with a different targeted therapy in each sub-study. The Phase 1b part of each applicable sub-study will evaluate the safety of the combination and select the dose for the Phase 2 part. The Phase 2 part of each sub-study will evaluate anti-tumor activity.
(Closed to Enrollment) Substudy A will enroll patients with recurrent or progressive melanoma or other solid tumors with BRAF fusion or CRAF/RAF1 fusions or amplification.
Substudy B will enroll patients with recurrent or progressive melanoma or other solid tumors with alterations in the key proteins of the MAPK pathway.
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
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent by participants ≥ 12 years of age either a Consent or an Assent Form will be provided to the patient based on their capacity, local regulations, and guidelines.
- •Participants must have a histologically confirmed diagnosis of melanoma or other solid tumor and a BRAF fusion, CRAF/RAF1 fusion, or CRAF/RAF1 amplifications obtained through a tumor or liquid biopsy as assessed by genomic sequencing, polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or another clinically accepted molecular diagnostic method recognized by local laboratory or regulatory agency.
- •Participants must have radiographically-recurrent or radiographically-progressive disease that is measurable using the appropriate tumor response criteria (e.g. RECIST version 1.1 or RANO).
- •Archival tumor tissue (preferably less than 3 years old) or fresh tumor tissue for correlative studies is required
- •If brain metastases are present, they must have been previously treated and be stable as assessed by radiographic imaging
排除标准
- •Prior therapy of any RAS-, RAF-, MEK-, or ERK-directed inhibitor therapy
- •Known presence of concurrent activating mutation
- •Participants with current evidence or a history of central serous retinopathy (CSR), retinal vein occlusion (RVO)
研究组 & 干预措施
Melanoma Cohort
Tovorafenib monotherapy
干预措施: Tovorafenib (Drug)
Tissue Agnostic Cohort
Tovorafenib monotherapy
干预措施: Tovorafenib (Drug)
结局指标
主要结局
Overall Response Rate (ORR) by the Investigator
时间窗: Up to 23 months
ORR was defined as the percentage of participants with the best overall confirmed response of complete response (CR) or partial response (PR) according to the appropriate response assessment criteria including Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for the disease setting as assessed by the Investigator. CR or PR was confirmed at a subsequent scan (\>=4 weeks) if the criteria for each are met . The exact 95% confidence intervals (CIs) were calculated using Clopper-Pearson method.
次要结局
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Up to 23 months)
- Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline(Baseline and up to 23 months)
- Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline(Baseline and up to 23 months)
- Duration of Response (DOR) in Participants With Best Overall Response(Up to 23 months)
- Duration of Progression Free Survival(Up to 23 months)
- Duration of Overall Survival(Up to 23 months)
- Time to Response(Up to 23 months)