In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 2504-2504
Abstract:
2504 Background: Isocitrate dehydrogenase 1 and 2 mutations (m IDH1/2) occur in approximately 70% and 4% of low-grade gliomas (LGGs), respectively, promoting oncogenesis via increased production of D-2-hydroxyglutarate. In this ongoing phase 1 trial, VOR, a potent, oral, reversible, brain-penetrant, first-in-class dual inhibitor of mIDH1/2, is being evaluated in advanced m IDH1/2 solid tumors, including gliomas. Safety and preliminary results were presented previously (Mellinghoff et al., J Clin Oncol 2018). Here, we report updated data for the non-enhancing glioma pt population. Methods: Pts with recurrent/progressive m IDH1/2 glioma received VOR daily (continuous 28-day cycles). Key eligibility criteria included: ≥18 years; histologically or cytologically confirmed glioma with documented m IDH1/2; ECOG 0-2; and evaluable disease by RANO-LGG criteria. Dose escalation cohorts enrolled using a Bayesian logistic regression model (BLRM) escalation guided by the overdose control (EWOC). Tumor response was evaluated by MRI every 8 weeks using RANO-LGG criteria by local assessment. Results: As of 28 Nov 2019, 22 pts with non-enhancing glioma had received VOR and 8 (36%) remain on treatment. M/F, 8/14; grade 2/3, 17/5; median age, 47 years; m IDH1/2, 20/1; 1p19q intact, 9/22; median (range) number of prior systemic therapies, 2 (1–4). Common (≥5 pts) treatment-emergent adverse events (AEs) of any grade and regardless of causality included increased ALT/AST (63.6%/59.1%), headache (45.5%), nausea (40.9%), neutropenia (31.8%), fatigue and hyperglycemia (27.3% each), and seizures and decreased white blood cell count (22.7% each). Transaminase elevations were grade 1 in severity at dose levels 〈 100mg and were less frequent (5 [38.5%] of 13 pts). Three subjects had related grade ≥3 AEs; 2 discontinued due to AEs. Objective response rate was 13.6% (1 partial response, 2 minor responses), and 17 (77.3%) pts achieved stable disease. 60.5% of pts were progression free and alive at 24 months. Conclusions: In this previously treated population with non-enhancing glioma, VOR was associated with a favorable safety profile. The study results also show encouraging preliminary activity within that population, with PFS duration extending to 24 months or longer in 60% of participants. A global randomized phase 3 study of VOR in grade 2 non-enhancing glioma pts who have had surgery only is currently enrolling (NCT04164901). Clinical trial information: NCT02481154 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.2504
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
detail.hit.zdb_id:
604914-X
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