Background H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma. Methods ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international Phase 3 study of ONC201 in newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on two consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS); PFS is assessed by response assessment in neuro-oncology-high grade glioma criteria (RANO-HGG) by blind independent central review. Secondary objectives include safety, additional efficacy endpoints, clinical benefit, and quality of life. Eligible patients have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility is not restricted by age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in multiple international sites.

中文翻译：

---

行动：ONC201（dordaviprone）在新诊断的 H3 K27M 突变弥漫性胶质瘤患者中进行的一项随机 3 期研究

背景 H3 K27M 突变型弥漫性胶质瘤主要影响儿童和年轻人，预后不良，目前尚无有效的全身治疗方法。ONC201（dordaviprone）此前已证明对复发性疾病患者有效。这项 3 期试验评估 ONC201 在新诊断的 H3 K27M 突变神经胶质瘤患者中的作用。方法 ACTION (NCT05580562) 是一项 ONC201 治疗新诊断的 H3 K27M 突变弥漫性胶质瘤的随机、双盲、安慰剂对照、平行组国际 3 期研究。已完成标准一线放疗的患者按 1:1:1 随机分配接受安慰剂、每周一次多达维酮或连续两天每周两次多达维酮。主要疗效终点是总生存期（OS）和无进展生存期（PFS）；PFS 通过盲法独立中央审查根据神经肿瘤学高级别神经胶质瘤标准 (RANO-HGG) 的反应评估进行评估。次要目标包括安全性、额外疗效终点、临床效益和生活质量。符合条件的患者具有组织学证实的 H3 K27M 突变弥漫性胶质瘤、Karnofsky/Lansky 体能状态≥70，并完成了一线放疗。资格不受年龄限制；然而，患者在随机分组时体重必须≥10 kg。患有原发性脊柱肿瘤、弥漫性内源性脑桥神经胶质瘤、软脑膜疾病或脑脊液播散的患者不符合资格。ACTION 目前正在多个国际网站上注册。