1980P - Artificial intelligence analysis shows enhanced CCNG1 expression in sarcoma tumors, a novel biomarker for DeltaRex-G tumor targeted retrovector encoding a CCNG1 inhibitor gene

Background

In phase 1/2 studies using DeltaRex-G targeted retrovector bearing a CCNG1 inhibitor gene for advanced sarcoma, long term survival reports showed that four (7%) patients with chemotherapy resistant advanced sarcoma were alive > 10 years from DeltaRex-G treatment initiation. Expanded access for DeltaRex-G, is currently open for advanced sarcoma patients. (NCT04091295). In this study, we analyzed CCNG1 expression in tumors of patients who are being followed at our Cancer Center to identify those who might respond favorably to DeltaRex-G therapy.

Methods

Archived formalin-fixed paraffin embedded (FFPE) tumor specimens (n=65) from patients with sarcoma were collected, processed, and subjected to RNA sequencing. Briefly, RNA-seq libraries were sequenced to generate 50 million reads that were aligned using Kallisto v0.42.4 to GENCODE v23 transcripts with default parameters. A gene expression level is presented as low/medium/high depending on the expression level of a such gene in patients of the reference cohort. Low = <17%; Medium = 17%-83%; High = >83%.

Results

Thirty male and 35 female subjects, ages ranging from 16 to 87 years were studied. Four (6%) tumors showed high CCNG1 expression, forty-seven (72%) tumors had medium expression, and fourteen (22%) tumors had low CCNG1 expression. Seven of 65 patients had osteosarcoma, of which 4 were male, three females, ages ranging from 16 to 57 years. The osteosarcoma tumors showed 86% with medium CCNG1 expression and 14% with low CCNG1 expression. Five patients with medium CCNG1 expression had metastatic disease while one patient with low and one with medium CCNG1 expression had localized disease. Of note, one participant with advanced chondrosarcoma had clinical benefit (stable disease) by RECISTv1.1 and is alive 3 years after DeltaRex-G treatment initiation. AI analysis of his tumor showed 74% CCNG1 expression.

Conclusions

Taken together, these data suggest that (1) 90% of sarcoma tumors have high to medium CCNG1 expression and (2) Four of 5 (80%) osteosarcoma tumors have medium CCNG1 expression. Prospective studies are planned to correlate CCNG1 expression level with response to DeltaRex-G therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Sarcoma Oncology Research Center.

Funding

Has not received any funding.

Disclosure

Z. Shekhovtsova: Financial Interests, Institutional, Officer: Boston Gene, Inc. K. Suryamohan: Other, Institutional, Officer: Boston Gene, Inc. E.M. Gordon: Financial Interests, Personal, Ownership Interest: Delta Next-Gene, LLC. All other authors have declared no conflicts of interest.