Arrillaga-Romany Isabel, Lassman Andrew, McGovern Susan L, Mueller Sabine, Nabors Burt, van den Bent Martin, Vogelbaum Michael A, Allen Joshua E, Melemed Allen S, Tarapore Rohinton S, Wen Patrick Y, Cloughesy Timothy
Mass General Cancer Center, Neuro-Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Columbia University Vagelos College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, New York-Presbyterian Hospital, New York City, New York, USA.
Neuro Oncol. 2024 May 3;26(Supplement_2):S173-S181. doi: 10.1093/neuonc/noae031.
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.
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 2 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.
H3 K27M突变型弥漫性胶质瘤主要影响儿童和年轻成年人，预后较差，目前尚无有效的全身治疗方法。ONC201（多德伐普隆）此前已在复发性疾病患者中显示出疗效。这项3期试验评估了ONC201在新诊断的H3 K27M突变型胶质瘤患者中的疗效。
ACTION（NCT05580562）是一项随机、双盲、安慰剂对照、平行组的国际3期研究，旨在评估ONC201在新诊断的H3 K27M突变型弥漫性胶质瘤中的疗效。完成标准一线放疗的患者按1:1:1随机分组，分别接受安慰剂、每周一次的多德伐普隆或连续两天每周两次的多德伐普隆。主要疗效终点是总生存期（OS）和无进展生存期（PFS）；PFS由盲法独立中央审查根据神经肿瘤学高级别胶质瘤标准（RANO-HGG）进行反应评估。次要目标包括安全性、其他疗效终点、临床获益和生活质量。符合条件的患者需经组织学证实为H3 K27M突变型弥漫性胶质瘤，卡诺夫斯基/兰斯基功能状态≥70，并完成一线放疗。入选不受年龄限制；然而，患者在随机分组时体重必须≥10 kg。原发性脊柱肿瘤、弥漫性脑桥内在胶质瘤、软脑膜疾病或脑脊液播散的患者不符合条件。ACTION目前正在多个国际地点招募患者。
