Ctni-54. Response by Rano2.0 Criteria in Onc201 (dordaviprone)-treated Patients With Recurrent H3 K27m-mutant Diffuse Midline Glioma
Year: 2024
Type: conference-abstract
Abstract: PURPOSE Response assessment in neuro-oncology (RANO) 2.0 is a recently established response assessment for glial tumors that is agnostic to WHO grade. This updated response assessment includes quantitative evaluation of enhancing and non-enhancing disease and recommendations to account for pseudoprogression. This analysis evaluated response to ONC201 by RANO2.0 in recurrent, H3K27M-mutant diffuse midline glioma (DMG), which was previously assessed by RANO-HGG/RANO-LGG (Arrillaga-Romany, JCO, 2024). METHODS Fifty patients with recurrent H3 K27M-mutant DMG were selected based on criteria designed with input from regulators to evaluate objective response to ONC201 monotherapy. Patients had contrast-enhancing, measurable, progressive disease, and were ≥90 days from radiation, with adequate washout from other anti-cancer therapies. Diffuse intrinsic pontine glioma, primary spinal tumors, leptomeningeal spread, or CSF-disseminating tumors were ineligible. Response was assessed using RANO2.0 criteria by two-party blinded independent central review. RESULTS Best response by RANO2.0 included one complete response (CR, 2.0%), nine partial responses (PR, 18.0%), and four minor responses (MR, 8.0%). Overall response rate (CR+PR+MR) by RANO2.0 criteria was 28.0% (n=14; 95%CI, 16-42). Disease control rate (CR+PR+MR+SD) was 40.0% (n=20; 26-55). Median duration of response was 10.4 months (95%CI, 7.4-15.4). Median time to response was 4.6 months (range, 1.6-15.9). 6- and 12-month progression free survival rates were 32.0% (95%CI, 19-47) and 27.0% (15-41), respectively. RANO2.0 response as a time-varying covariate was significantly associated with overall survival in a multivariate analysis considering baseline performance score, multiple enhancing target lesions, enhancing tumor size, and number of prior recurrences (HR [95%CI], 0.22 [0.08–0.58]; p=0.0023). Patients with an objective response by RANO2.0 were more likely to be alive at 12 (100%) and 24 (86%) months, have reduced corticosteroid usage, and have improved performance status. Responses occurred at a higher rate among patients with a higher performance score and fewer target lesions. CONCLUSIONS RANO2.0 assessment of ONC201-treated patients suggests durable and clinically meaningful efficacy in recurrent H3K27M-mutant DMG.
Source: Neuro-Oncology
Authors: Timothy Cloughesy, Joshua E Allen, Isabel Arrillaga-Romany, Marissa Barbaro, Tracey T Batchelor, Nicholas Butowski, Andrew Cluster, John de Groot, Jerome Graber, Aya M Haggiagi, Lindsay B Kilburn, Sylvia C Kurz, Allen S Melemed, Samuel C Ramage, Michael E Salacz, Nicole Shonka, Ashley Sumrall, Rohinton Tarapore, Lynne Taylor, Patrick Wen
Institutions: University of California, Los Angeles, Chimerix (United States), Massachusetts General Hospital, NYU Langone Health, Dana-Farber Brigham Cancer Center, University of California, San Francisco, Washington University in St. Louis, University of Washington Medical Center, Fred Hutch Cancer Center, Columbia University Irving Medical Center, Yale Cancer Center, Cooper University Hospital, University of Nebraska Medical Center, Levine Cancer Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4404237689