In:
Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii51-ii51
Abstract:
The nitrone compound OKN-007 is a novel anti-cancer agent. In glioblastoma xenografts, OKN-007 reduces cell proliferation and angiogenesis, and increases apoptosis. Here we report on the safety, efficacy, and pharmacokinetics (PK) of OKN-007 in adults with recurrent glioma. METHODS NCT01672463 is a phase 1b trial of OKN-007 in adults with recurrent gliomas previously treated with standard therapy. OKN-007 was administered by IV. The study comprised a 3 + 3 dose escalation design followed by an expansion cohort at the maximum tolerated dose (MTD). The dose escalation drug levels were 20 (n = 3), 40 (n = 3), and 60 mg/kg (n = 3), treating on a schedule of thrice weekly for 4 weeks, then twice weekly for 4 weeks, then once weekly until progression. Drug PK was determined in the dose escalation cohorts. The expansion cohort was treated with 60 mg/kg thrice weekly for 12 weeks, then twice weekly for 12 weeks, then once weekly until progression (n = 6). Kaplan-Meier analysis was used to determine progression-free (PFS) and overall survival (OS). RESULTS Median age was 51 years (range, 25–62). No dose-limiting toxicities were observed. The expansion dose was 60 mg/kg. Of 123 adverse events (AEs), 34 were deemed probably (1.6%) or possibly (26%) treatment-emergent (TEAE). The most commonly-occurring TEAEs were fatigue (4.1%) and headache (3.3%). Grade 3 TEAEs included headache, urinary tract infection, and increased prothrombin time (0.8% each). Two grade 1 AEs, hypokalemia and dizziness, were considered probably attributable to OKN-007. In patients receiving 60 mg OKN-007/kg, median PFS was 1.4 months and OS was 21 months (log rank p = 0.08 for comparison across doses). Systemic PK exposure was dose proportional. The average half-life of OKN-007 is 2.8 hours. CONCLUSIONS OKN-007 appears safe and, compared to standard therapy, may prolong OS in recurrent glioma.
Type of Medium:
Online Resource
ISSN:
1522-8517
,
1523-5866
DOI:
10.1093/neuonc/noaa215.206
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
2094060-9
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