LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic Therapy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 418
- 试验地点
- 218
- 主要终点
- Objective response rate (ORR) of tovorafenib monotherapy versus SoC chemotherapy
研究概览
简要总结
This is a 2-arm, randomized, open-label, multicenter, global, Phase 3 trial to evaluate the efficacy, safety, and tolerability of tovorafenib monotherapy versus standard of care (SoC) chemotherapy in participants with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring first-line systemic therapy.
详细描述
Approximately 400 treatment-naïve LGG participants will be randomized 1:1 to either tovorafenib (Arm 1) or an Investigator's choice of SoC chemotherapy (Arm 2).
Arm 1 (tovorafenib): Treatment cycles will repeat every 28 days in the absence of disease progression. Participants will continue tovorafenib until any of the following occurs: disease progression, unacceptable toxicity, withdrawal of consent to treatment, or end of study.
Arm 2 (Investigator's Choice of SoC Chemotherapy): Participants will receive one of 4 SoC chemotherapy options selected by the treating Investigator: Children's Oncology Group - Vincristine/Carboplatin (COG-V/C) regimen, International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C) regimen, vinblastine (VBL) regimen, or monthly carboplatin. The choice of SoC chemotherapy regimen will be selected prior to participant randomization. Treatment will continue until completion of therapy or until any of the following occurs: disease progression, unacceptable toxicity, withdrawal of consent to treatment, or end of study.
Participants who discontinue treatment due to disease progression will have (1) radiographic evidence of disease progression, as determined by the Investigator, or (2) clinical progression, as determined by the Investigator. Investigators are encouraged to discuss cases of clinical progression and early radiographic progression without clinical symptoms with the Sponsor Medical Monitor prior to treatment discontinuation or initiation of a different form of treatment for the malignancy. Participants may continue therapy beyond progressive disease (PD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Less than 25 years of age with LGG with known activating RAF alteration.
- •Histopathologic diagnosis of glioma or glioneuronal tumor.
- •At least one measurable lesion as defined by RANO criteria.
- •Meet indication for first-line systemic therapy.
排除标准
- •Participant has any of the following tumor-histological findings:
- •Subependymal giant cell astrocytoma (Tuberous Sclerosis)
- •Diffuse intrinsic pontine glioma, even if histologically diagnosed as World Health Organization (WHO) Grade I-II
- •Participant's tumor has additional pathogenic molecular alterations, including but not limited to a) isocitrate dehydrogenase (IDH) 1/2 mutation, b) Histone H3 mutation, and c) neurofibromatosis Type 1 (NF-1) loss of function alteration.
- •Known or suspected diagnosis of NF-1/ neurofibromatosis Type 2 (NF-2).
- •Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/IV targeted therapy) including radiation.
研究组 & 干预措施
Tovorafenib
干预措施: Tovorafenib (Drug)
Investigator's choice of Standard of care therapy
干预措施: Chemotherapeutic Agent (Drug)
结局指标
主要结局
Objective response rate (ORR) of tovorafenib monotherapy versus SoC chemotherapy
时间窗: Up to 60 months
ORR assessed per Response Assessment in Pediatric Neuro Oncology (RAPNO) criteria by Independent Review Committee (IRC), and defined as the proportion of participants with overall confirmed response of complete response (CR), partial response (PR), or minor response (MR).
次要结局
- Progression-free survival (PFS) of tovorafenib monotherapy versus SoC chemotherapy(Up to 60 months)
- Change in best corrected visual acuity of tovorafenib monotherapy versus SoC chemotherapy in OPG participants aged ≥ 3 years(Baseline and up to 5 years)
- Visual progression-free survival (v-PFS) of tovorafenib monotherapy versus SoC chemotherapy(Up to 60 months)
- PFS of tovorafenib monotherapy versus SoC chemotherapy(Up to 60 months)
- Event-free survival (EFS) of tovorafenib monotherapy versus SoC chemotherapy(Up to 60 months)
- Overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy(Up to 60 months)
- Number of participants with any treatment-emergent adverse events, and Serious adverse events(Up to 60 months)
- . Number of participants with clinically significant vital signs and laboratory abnormalities findings(Up to 60 months)
- Change from baseline in Adaptive Behavior Composite Score (ABS) of tovorafenib monotherapy versus SoC chemotherapy(Baseline, Year 1, 2 and 5)
- Change from baseline in the Motor Skills Domain Score of tovorafenib monotherapy versus SoC chemotherapy(Baseline, Year 1, 2 and 5)
- Change from baseline in the Communication Domain Score of tovorafenib monotherapy versus SoC chemotherapy(Baseline, Year 1, 2 and 5)
- Change from baseline in the Daily Living Domain Score of tovorafenib monotherapy versus SoC chemotherapy(Baseline, Year 1, 2 and 5)
- Change from baseline in the Socialization Domain Score of tovorafenib monotherapy versus SoC chemotherapy(Baseline, Year 1, 2 and 5)
- Change in age-adjusted visual acuity (VA) of tovorafenib monotherapy versus SoC chemotherapy in optic pathway glioma (OPG) participants aged < 3 years(Baseline and up to 5 years)
- ORR of tovorafenib monotherapy versus SoC chemotherapy(Up to 60 months)
- Change from Baseline in health-related quality of life (HRQoL) total score of tovorafenib monotherapy versus SoC chemotherapy(Baseline, Year 1, 2 and 5)
- Clinical benefit rate (CBR) of tovorafenib monotherapy versus SoC chemotherapy(Up to 60 months)
- Time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy(Up to 60 months)
- EFS of tovorafenib monotherapy versus SoC chemotherapy(Up to 60 months)
- Duration of response (DOR) of tovorafenib monotherapy versus SoC chemotherapy(Up to 60 months)