Tumor Agnostic Deltarex-G+ Gene Therapy Demonstrates Activity in Breast, Pancreatic, Sarcoma Cancers

CCNG1-targeted Deltarex-G gene therapy plus an FDA approved drug (Deltarex-G+) showed some evidence of response in patients’ tumors, including pancreatic cancer, breast cancer, and sarcoma. All tested tumors had enhanced CCNG1 expression.¹

Data from the BLESSED expanded access study (NCT04091295) were presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, by Erlinda Gordon, MD, founder and president, Aveni Foundation, and director, biological and immunological therapies, and chairman, institutional biosafety committee director, Cancer Center of Southern California/Sarcoma Oncology Center, and founder, chief operating officer, and FDA liaison, Counterpoint Biomedica.

“Deltarex-G is the only tumor targeted gene therapy that can be injected intravenously and it in vivo gets into the tumor microenvironment by binding to abnormal signature proteins in the tumor. So, it's unlike the ex vivo gene therapies for cancer... it's an off the shelf gene therapy product that has a navigation system that goes to the tumor itself,” Gordon told CGTLive during the meeting. “We tested that... CCNG1 is present in all the tumor types that we have tested including sarcoma, pancreatic cancer, breast cancer, testicular cancer, bladder cancer, so that we think it's a tumor agnostic therapy, rather than looking for a very rare oncogene to target."

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Deltarex-G is a tumor-targeted retro vector that encodes a cell cycle cyclin G1 (CCNG1) inhibitor gene. Gordon and colleagues, in partnership with BostonGene, screen 139 tumors for CCNG1 expression and found it to be enhanced in all, with levels ranging from 35-89%. The tumors were characterized as having high CCNG1 expression (n = 31; 22%), medium-high expression (n = 49; 35%), medium-low expression (n = 53; 38%), or low expression (n = 6; 5%). Most patients (n = 172; 73%) had metastatic disease, 37 (27%) had localized disease, and no correlation was found between CCNG1 expression and disease stage.¹

“CCNG1 is not usually reported by molecular profiling companies except for BostonGene which is why they are our partners.... even though I tried to explain it to [other] next-generation sequencing (NGS) companies, they will not record it, even though there is a clinical trial [ongoing],” Gordon said. Deltarex-G is the first program to target CCNG1, despite an apparent (but under reported) ubiquity.

Data were also reported from 9 patients treated with Deltarex-G+. Four treated between 2008 and 2021 had advanced pancreatic cancer, HR+Her+ invasive breast cancer, triple-negative breast cancer, and squamous cell carcinoma with CCNG1 expression levels of 24, 23, 74, and 40%, respectively. These patients remain alive 15, 3, 2.5, and 2.5 years after treatment initiation, respectively, with 3 patients having sustained remission (1 with pancreatic, 2 with breast).¹

Five patients are currently receiving treatment with Deltarex-G+ and remain alive 5.1 to 7.7 months since treatment initiation. One patient with advanced breast cancer had a partial response, 1 with advanced pancreatic cancer had stable disease, and 3 with sarcoma had stable disease. No serious adverse events have been reported.¹

The therapy “does not have systemic toxicity”, Gordon said.

Gordon and colleagues concluded their poster by asserting that Deltarex-G is a promising therapy and phase 2/3 studies are warranted to confirm its efficacy and safety. Deltarex-G has previously demonstrated safety and activity in phase 1/2 studies.²

“Rare diseases like pancreatic cancer are a death sentence, and sarcoma occurs in mostly in adolescents and young adults,” Gordon added, urging the need for further investigation in this area.

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REFERENCES

1. Jeffrey S, Omelchenko N, Kumar V, et al. Deltarex-G Plus (Deltarex-G + FDA Approved Drug) Demonstrates Clinical Benefit in Advanced Chemoresistant Pancreatic Cancer, Sarcoma, and Breast Cancer (NCT04091295). Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #1407
2. Bruckner HW, Chawla SP, Omelchenko N, et al. Phase I-II study using DeltaRex-G, a tumor-targeted retrovector encoding a cyclin G1 inhibitor for metastatic carcinoma of breast. Front. Mol. Med, 2023 (3). doi: 10.3389/fmmed.2023.1105680