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International Precision Medicine Conference

April 19-21, 2021 | Orlando, USA

Scopus Indexed Conference
scopus
Holiday Inn Orlando SW Celebration Area, 5711 W. Irlo Bronson Memorial Highway, Kissimmee, FL 34746, USA
Phone : 1 (702) 988 2320
Toll Free: 1800–883-8082
Whatsapp: +1 (540) 709-1879
Email: precision@magnus-event.com
April 19-21, 2021 | Orlando, USA

Fatih Uckun

International Precision Medicine Conference- Fatih Uckun
Fatih Uckun
Oncotelic, USA
Title : Targeting high-grade anaplastic astrocytoma and glioblastoma with a first-in class anti-tgf?2 RNA therapeutic administered by convection-enhanced delivery

Abstract:

Transforming growth factor beta 2 (TGFβ2) has been implicated as a key contributor to the immunosuppressive landscape of the tumor microenvironment (TME) in high-grade gliomas (HGG) that is characterized by a T-cell exhaustion signature and pronounced T-cell hyporesponsiveness.   OT-101 is a first-in-class RNA therapeutic designed to abrogate the immunosuppressive actions of TGFβ2.  This plenary presentation will detail the safety profile and clinical single agent activity of OT-101 in a Phase 2 clinical trial.  OT-101 was administered via high-flow microperfusion with an intratumoral catheter using a convection enhanced delivery (CED) system. 77 patients (Efficacy Population) received 4-11 cycles of OT-101 via continuous infusion over 7 days (d). 26 patients (33.8%) had marked reductions of their tumor volume after receiving OT-101: 19 achieved durable objective responses (CR: 3, PR: 16).  The average (Mean ± SE) percent reduction for the 19 responders was 91.9 ± 2.6 (Median = 95.7, Range: 57.5-100). Six patients achieved 100% reduction in tumor volume over the course of the treatment.   The median time for 90% reduction of the baseline tumor volume was 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. 7 had stable disease (SD) lasting >6 months.  The median progression-free survival (PFS) (1109d [95% CI: 992 -  >1423] vs. 37d [95% CI: 35 – 59]  (Log-rank Chi Square = 69.9, P-value <0.0001) and overall survival (OS) (1280d [95% CI: 1116 -  >1743] vs. 240d [95% CI: 169 – 361]  (Log-rank Chi Square = 47.0, P-value <0.0001) of these 26 patients (GBM:10, AA:16) with favorable responses was significantly better than the PFS or OS of the remaining 51 patients.  The final generalized linear model (GLM) for best overall response (BOR) (Binomial distribution, chi-square value = 39.7, df = 12, P<.0001) and OS model (loglogistic best fit highly significant with a chi-square value = 56.0, df = 12, P<0.0001) identified 3 significant predictors: Baseline KPS score (P[BOR] = 0.011; P[OS] = 0.0004), cancer subtype (P[BOR] = 0.017,  P[OS] = 0.036) and steroid use (P[BOR] = 0.0067, P[OS] = 0.0022).  Being an AA rather than a GBM patient, having a higher baseline KPS score, receiving either no steroids or short-term steroids during management of AE were associated with favorable responses and improved OS for R/R GBM/AA patients treated with OT-101 as a single agent. These results demonstrate that OT-101, when administered via CED as second line therapy exhibits clinically meaningful single-agent activity and induces durable CR/PR/SD in R/R HGG patients.

Audience Take Away:

  • The audience will learn about RNA therapeutics as a new class of precision medicines
  • The audience will learn about the treatment options for high-grade gliomas
  • The insights and lessons learned in our study will help the participants in their clinical research and design of safe and effective treatment strategies for therapy of brain tumors. 
  • The audience will learn of the immunosuppressive functions of TGF and the emerging role of TGF as a molecular target for immune-oncology drugs for treatment of solid tumors as well as hematologic malignancies.

Biography:

Dr. Uckun is an experienced hematologist-oncologist who is an elected active member of ASCI, an honor society for physician-scientists and he currently serves as the Chief Medical Officer of Oncotelic. He earned his doctoral degrees at University of Heidelberg in Germany and completed his clinical residency and fellowship training at the University of Minnesota in the USA.  He served as a Professor both at the University of Minnesota and at the University of Southern California.  He has authored more than 500 peer-reviewed publications and received numerous awards including the Stohlman Memorial Award of the Leukemia Society of America.

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