Effect of DeltaRex-G ± DeltaRex-G Plus (an FDA-approved drug) on advanced chemoresistant pancreatic cancer, sarcoma, and breast cancer.

person Neal Shiv Chawla City of Hope Comprehensive Cancer Center, Duarte, CA info_outline Neal Shiv Chawla, Samantha Jeffrey, Nadezhda Omelchenko, Rheanna Carter, Anmol Dia Agarwal, Ishrat Buhyian, William H. Isacoff, Michael Morse, William Swaney, Sant P. Chawla, Frederick L. Hall, Erlinda Maria Gordon

Authors person Neal Shiv Chawla City of Hope Comprehensive Cancer Center, Duarte, CA info_outline Neal Shiv Chawla, Samantha Jeffrey, Nadezhda Omelchenko, Rheanna Carter, Anmol Dia Agarwal, Ishrat Buhyian, William H. Isacoff, Michael Morse, William Swaney, Sant P. Chawla, Frederick L. Hall, Erlinda Maria Gordon Organizations City of Hope Comprehensive Cancer Center, Duarte, CA, Sarcoma Oncology Center, Santa Monica, CA, Sarcoma Oncology Research Center, Santa Monica, CA, BostonGene, Morgan Hill, CA, William H. Isacoff, MD, Inc, Santa Monica, CA, Duke University, Durham, NC, Expression therapeutics, Westchester, OH Abstract Disclosures Research Funding No funding sources reported Background: Expanded access for DeltaRex-G, a tumor targeted retrovector encoding a CCNG1 inhibitor, is being studied for advanced cancers. Methods: 137 archived tumor specimens were analyzed with AI RNA sequencing to identify CCNG1 expression levels, reported as: Low = 17%, Medium-low = 17%-49%, Medium-high = 50%-83%, High = 83%. Nine patients with advanced solid malignancies, whose CCNG1 levels were identified, received DeltaRex-G (2-3 x 10e11 cfu/dose one to three times a week), either without an FDA-approved drug, or with an FDA-approved drug (“DeltaRex-G Plus”). Overall survival, duration of treatment, and responses were evaluated. Results: All analyzed tumors showed enhanced CCNG1 expression. Thirty (22%) tumors exhibited High CCNG1 expression, 48 (35%) showed Medium-High CCNG1 expression, 53 (39%) displayed Medium-Low CCNG1 expression, and six (4%) had Low CCNG1 expression. One hundred (73%) patients had metastatic disease, and 37 (27%) had localized disease. There was no correlation between CCNG1 expression and disease stage. Four patients with advanced pancreatic cancer (n = 1), Stage 1 HR+Her2+ invasive breast cancer (n = 1), Stage 1 triple negative breast cancer (n = 1), and squamous cell carcinoma of skin (n = 1), received DeltaRex-G alone or DeltaRex-G Plus between 2008 and 2021 and are alive 15, 3, 2.5, and 2.5 years since treatment initiation, respectively. Retrospective analysis of their respective tumors showed CCNG1 expression levels of 24%, 23%, 74%, and 40%. Three of the patients are in sustained remission and the patient with squamous cell carcinoma had a partial response. Of the five patients currently being treated with DeltaRex-G Plus: one patient with advanced breast cancer had a partial response (n = 1), one patient with advanced pancreatic cancer (n = 1) and three patients with soft tissue sarcoma (n = 3) had stable disease. Four of five patients had previously progressed with standard doses of chemotherapy. All patients are alive from 11 to 22 weeks since treatment initiation. No serious treatment-related adverse events have been reported. Conclusions: Taken together, the data shows that (1) 100% of 137 tumors tested have enhanced CCNG1 expression, further reinforcing the 2021 FDA-CBER authorization for use of DeltaRex-Plus, and (2) DeltaRex-G Plus is a promising therapy for advanced pancreatic cancer, sarcoma, and breast cancer. Randomized Phase 2/3 studies are warranted to confirm the efficacy and safety of DeltaRex-G Plus. Clinical trial information: NCT04091295.

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