Abstract 2757
Background
SOM is a devasting consequence of CRT. hTFF1 is a naturally occurring protein that can protect the mucosa. LLB were genetically modified (GM) to produce hTFF1, formulated as an oral rinse and attenuated SOM in patients receiving chemotherapy. The GM LLB lack all necessary components for survival and multiplication. The objective of this ongoing Phase 2 trial is to assess the safety and efficacy of AG013 as a SOM intervention.
Methods
This is a double-blind, randomized, placebo-controlled trial recruiting ∼200 patients with OCOPC at 48 sites (US and Europe). Patients (PTS) receive cumulative RT (cumRT) between 50 Gy – 72 Gy, 2.0-2.2 Gy QD + QW/Q3W cisplatin. At least two mucosal sites at risk of SOM receive minimal cumRT of 50 Gy. PTS are randomized 1:1 to receive placebo or AG013 [LLB strain sAGX0085 engineered to secrete hTFF1 (2x1011 CFU/15 mL tid)] starting on CRT day 1 and continuing 2 weeks post-CRT. Beginning on CRT day 1 and continuing Q2W until resolution, OM is assessed by trained assessors and scores assigned centrally. The primary and secondary efficacy endpoints are SOM duration and incidence (WHO criteria). AEs are described by NCI-CTCv4. A DSMB performed a safety analysis following accrual of the first 24 PTS. Tumor response to CRT is evaluated for 1-year post CRT.
Results
71 PTS have been randomized across 48 study sites. Complete OM data are available for 42 PTS for whom blinded evaluation (active and placebo) demonstrated an overall SOM incidence of 52%. SOM was noted at 81 of 547 visits (14.8%). 25 PTS have stopped active treatment; 2 for non-compliance, 5 for AEs, and 18 lost to follow-up or unwilling or unable to conform to the protocol. Unexpected SAEs were noted in 9 PTS. No study drug-associated cases of bacteremia or sepsis were seen. DSMB review after the first 24 PTS concluded that there were no contraindications to study continuance.
Conclusions
Observations based on blinded data suggest that AG013 offers a safe, well-tolerated, and potentially efficacious platform to deliver an effective protein intervention for SOM mitigation.
Clinical trial identification
AG013-ODOM-201.
Editorial acknowledgement
Legal entity responsible for the study
Oragenics, Inc.
Funding
Oragenics, Inc.
Disclosure
S. Sonis: Advisory / Consultancy, consultant: Oragenics. All other authors have declared no conflicts of interest.
Resources from the same session
3664 - Longitudinal changes in cell-free DNA (cfDNA) methylation levels identify early non-responders to treatment in advanced solid tumors
Presenter: Andrew Davis
Session: Poster Display session 3
Resources:
Abstract
3212 - Multigene panel testing results for hereditary breast cancer in 1325 individuals: implications for gene selection and considerations for guidelines.
Presenter: Georgios Tsaousis
Session: Poster Display session 3
Resources:
Abstract
2591 - PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors
Presenter: Julia Quintanilha
Session: Poster Display session 3
Resources:
Abstract
4377 - ERBB2 mRNA as a predictor in HER2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC) treated with HER2 blockade in combination with endocrine therapy (ET): a retrospective analysis of the ALTERNATIVE and SOLTI-PAMELA trials.
Presenter: Nuria Chic
Session: Poster Display session 3
Resources:
Abstract
3439 - Early on-treatment vs pre-treatment tumor transcriptomes as predictors of response to neoadjuvant therapy for HER2-positive inflammatory breast cancer
Presenter: Sonia Pernas
Session: Poster Display session 3
Resources:
Abstract
2512 - AXL expression predicts poor prognosis and lack of efficacy of anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC)
Presenter: Claudia Cardone
Session: Poster Display session 3
Resources:
Abstract
4061 - Prevalence of EGFR mutations and its correlation with Egyptian patients’ human kinetics (PEEK Study)
Presenter: Adel Ibrahim
Session: Poster Display session 3
Resources:
Abstract
2547 - Evaluation of tumor microenvironment identifies immune correlates of response to combination immunotherapy with margetuximab (M) and pembrolizumab (P) in HER2+ gastroesophageal adenocarcinoma (GEA)
Presenter: Sergio Rutella
Session: Poster Display session 3
Resources:
Abstract
4671 - Clinicopathological and molecular criteria assessment for the screening of hypermutated proficient mismatch repair (pMMR) colorectal cancers (CRC) with exonucleasic domain POLE (edPOLE) mutations (mt).
Presenter: Benoit Rousseau
Session: Poster Display session 3
Resources:
Abstract
3862 - Tumor mutation burden and microsatellite instability in colorectal cancer
Presenter: Francesca Fenizia
Session: Poster Display session 3
Resources:
Abstract