12/10/2024
The current study OT-01-P201 (STOP-PC) is a follow-on phase 2/3 trial building on five previous clinical trials conducted in Korea, the US, and the EU. These include two phase 2 trials involving over 200 patients:
P001: A phase 2 trial assessing the safety and tolerability of OT-101 administered intravenously in patients with advanced tumors overproducing TGF-β2 (ClinicalTrials.gov ID: NCT00844064).
G004: A phase 2b trial evaluating the TGF-β2 antisense compound OT-101 in recurrent or refractory high-grade glioma (ClinicalTrials.gov ID: NCT00431561).
In these studies, OT-101 demonstrated clinical benefits in pancreatic ductal adenocarcinoma (PDAC), melanoma, and glioma, including documented cases of complete remission.
OT-101 works by adopting the patient’s immune system to target and eradicate tumors through the suppression of TGF-β2, a cytokine implicated in immune evasion and tumor progression.
Median survival for patients with low TGF-β2 expression was 72 months, compared to 15 months for those with high TGF-β2 levels.
When combined with irinotecan (a core component of the mFOLFIRINOX regimen), OT-101 extended median survival to over 34 months in patients with low TGF-β2 expression. Importantly, the modified FOLFIRINOX regimen (mFOLFIRINOX) used in STOP-PC has been shown to be safer while maintaining efficacy comparable to traditional FOLFIRINOX.
Recent developments further support OT-101's potential:
A phase 1b trial combining OT-101 with IL-2 in solid tumors identified an optimal dose of 140 mg/m².
New research highlights the critical role of TGF-β2 in the progression of various tumor types, including PDAC, suggesting OT-101 could significantly benefit these patients.
Given the clinical data and its novel mechanism of action, OT-101 holds great promise for improving outcomes in PDAC patients, particularly when integrated into combination therapies like mFOLFIRINOX.
2024 peer reviewed publications are available at Pubmed as follow:
1. TGFB2 mRNA Levels Prognostically Interact with Interferon-Alpha Receptor Activation of IRF9 and IFI27, and an Immune Checkpoint LGALS9 to Impact Overall Survival in Pancreatic Ductal Adenocarcinoma. Qazi S, Trieu V. Int J Mol Sci. 2024 Oct 18;25(20):11221. doi: 10.3390/ijms252011221. PMID: 39457004 (https://pubmed.ncbi.nlm.nih.gov/39457004/)
2. Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas. Trieu V, Maida AE, Qazi S. Cancers (Basel). 2024 Mar 19;16(6):1202. doi: 10.3390/cancers16061202. PMID: 38539537 Free PMC article. (https://pubmed.ncbi.nlm.nih.gov/38539537/)
3. Transforming Growth Factor Beta 2 (TGFB2) and Interferon Gamma Receptor 2 (IFNGR2) mRNA Levels in the Brainstem Tumor Microenvironment (TME) Significantly Impact Overall Survival in Pediatric DMG Patients. Qazi S, Talebi Z, Trieu V. Biomedicines. 2024 Jan 15;12(1):191. doi: 10.3390/biomedicines12010191. PMID: 38255296 Free PMC article. (https://pubmed.ncbi.nlm.nih.gov/38255296/)
4. High Intra-Tumor Transforming Growth Factor Beta 2 Level as a Predictor of Poor Treatment Outcomes in Pediatric Diffuse Intrinsic Pontine Glioma. Uckun FM, Qazi S, Trieu V. Cancers (Basel). 2023 Mar 9;15(6):1676. doi: 10.3390/cancers15061676. PMID: 36980562 Free PMC article. (https://pubmed.ncbi.nlm.nih.gov/36980562/)
