Reference Detail

Ref Type

Journal Article

PMID

(31795071)

Authors

Uckun FM, Qazi S, Hwang L, Trieu VN

Title

Recurrent or Refractory High-Grade Gliomas Treated by Convection-Enhanced Delivery of a TGFβ2-Targeting RNA Therapeutic: A Post-Hoc Analysis with Long-Term Follow-Up.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancers	11	12	2019 Nov 28		Cancers (Basel)

URL

Abstract Text

Background. OT101 is a first-in-class RNA therapeutic designed to abrogate the immunosuppressive actions of transforming growth factor beta 2 (TGFβ2). Here, we report our post-hoc analysis of the single-agent activity of OT101 in adult patients with recurrent and/or refractory (R/R) high-grade gliomas. Methods. In a Phase 2 clinical trial (ClinicalTrials.gov, NCT00431561), OT101 was administered to 89 R/R high-grade glioma (HGG) (anaplastic astrocytoma/AA: 27; glioblastoma multiforme/GBM: 62) patients with an intratumoral catheter using a convection enhanced delivery (CED) system. Seventy-seven patients (efficacy population; GBM: 51; AA: 26) received at least the intended minimum number of four OT101 treatment cycles. Response determinations were based on central review of magnetic resonance imaging (MRI) scans according to the McDonald criteria. Standard statistical methods were applied for the analysis of data. Findings. Nineteen patients had a complete response (CR) or partial response (PR) following a slow but robust size reduction of their target lesions (median time for 90% reduction of the baseline tumor volume = 11.7 months, range: 4.9-57.7 months). The mean log reduction of the tumor volume was 2.2 ± 0.4 (median = 1.4: range: 0.4-4.5) logs. In addition, seven patients had a stable disease (SD) lasting ≥6 months. For the combined group of 26 AA/GBM patients with favorable responses, the median progression-free survival (PFS) of 1109 days and overall survival (OS) of 1280 days were significantly better than the median PFS (p < 0.00001) and OS (p < 0.00001) of the non-responders among the 89 patients or the 77-patient efficacy population. Conclusion. Intratumorally administered OT101 exhibits clinically meaningful single-agent activity and induces durable CR/PR/SD in R/R HGG patients.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References