CTNI-49 - Early signal of activity from a phase 2 study of ST101, a first-in-class peptide antagonist of CCAAT/enhancer-binding protein ² (C/EBP²), in recurrent glioblastoma (GBM).

Friday, November 18, 2022

7:30 PM – 9:30 PM ET

Location: West/Central Hall

Poster Presenter(s)

Fabio Iwamoto, MD

Columbia University Medical Center
New York, United States

Author(s)

Vinai Gondi, MD

Northwestern Medicine Cancer Center Warrenville
Warrenville, United States
Nicholas A. Butowski, MD

Department of Neurological Surgery, University of California San Francisco
San Francisco, United States
GF

Gerald S. Falchook, MD

Sarah Cannon Research Institute at HealthONE
Denver, United States
AW

Anja Williams

Sarah Cannon UL and UCL, London
London, United Kingdom
Katherine B. Peters, MD, PhD

The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center
Durham, United States
JE

Jeff Evans, MD

University of Glasgow and Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
NL

Nehal Lakhani, MD, PhD

START Midwest
Grand Rapids, United States
MM

Meredith McKean, MD, MPH

Sarah Cannon Research Institute, Tennessee Oncology
Nashville, United States
Stefan N. Symeonides, MD, PhD

Edinburgh Cancer Research Centre, University of Edinburgh
Edinburgh, United Kingdom
Benjamin M. Ellingson, PhD

University of California Los Angeles
Los Angeles, United States
Jim Rotolo, PhD

Sapience Therapeutics Inc
Harrison, United States
GC

Gina Capiaux, PhD

Sapience Therapeutics Inc
Harrison, United States
EW

Erol Wiegert

Bexon Clinical Consulting
Montclair, United States
RM

Rob Michel

Bexon Clinical Consulting
Montclair, United States
SK

Steve Kaesshaefer, MBA

Bexon Clinical Consulting
Monclair, United States
AB

Alice Bexon, MD

Bexon Clinical Consulting
Montclair, United States

Background: C/EBPβ is a transcription factor that is active during embryofetal development but held in an inactive state in most mature cells (Zahnow 2009). C/EBPβ activates a proliferation/survival gene signature in multiple cancers, where it inversely correlates with disease prognosis and survival. ST101 is a cell-penetrating peptide antagonist of C/EBPβ. ST101 exposure leads to selective tumor cell death in multiple human cancer cell lines, including GBM, without impacting normal cell viability. In vivo, ST101 displays rapid uptake into multiple organs, the ability to cross the blood-brain barrier, and a long plasma half-life due to its resistance to degradation. It has potent anti-tumor activity in multiple GBM models, as a single agent or in combination, which supported moving into clinical development. TRIAL

Design: This phase 2 study is enrolling adult patients with GBM that has recurred or progressed after one standard treatment regimen (surgery, radiotherapy +/-temozolomide). Patients require measurable disease at baseline and at least 3 months from prior radiotherapy. Subjects receive the recommended phase 2 dose of ST101 (500mg IV weekly). Recruitment in the phase 2 portion of this trial began in January, 2022.

Results: As of June 1, 2022, 14 GBM patients were enrolled. One patient has a confirmed mRANO partial response (PR) after 18 weeks of therapy, seven patients have not reached the first on-study assessment and six patients progressed. The median duration of therapy was 5 weeks. ST101 has a favorable safety profile with minor infusion related reactions being the most common adverse event. Based on the confirmed PR, the GBM cohort will be expanded.

Conclusion: This first-in-class C/EBPβ inhibitor, ST101, showed an early signal of activity in recurrent GBM. More extensive follow-up and clinical experience will be presented as this trial expands and matures.