(P 106) DELTAREX-G, A TUMOR TARGETED CCNG1 INHIBITOR, DEMONSTRATES CLINICAL BENEFIT IN ADVANCED CHEMORESISTANT SARCOMA FOLLOWING FDA CBER AUTHORIZATION FOR USE AS PLATFORM THERAPY WITH FDA APPROVED DRUGS

Objective: CCNG1 is an inducible proto-oncogene, with enhanced expression levels reported in a variety of solid malignancies, and most recently, sarcoma. Expanded access for DeltaRex-G, a tumor targeted retrovector encoding a dominant negative CCNG1 gene, is on-going for an intermediate-sized population of advanced sarcoma (NCT04091295). This study presents (1) the retrospective analysis of CCNG1 expression levels in archived sarcoma tumor specimens and (2) the clinical progress of sarcoma patients currently receiving DeltaRex-G therapy.

Methods: (1) Formalin-fixed paraffin-embedded sarcoma tumor specimens (n=179) of patients who are actively followed at the Sarcoma Oncology Center were assessed for CCNG1 expression level by RNA analysis. Expression was quantified as transcripts per million (TPM) and log-2 transformed. Expression is presented in relation to the distribution of TPM values in the reference cohort of sarcoma patients. Expression levels are categorized as Low (< 17%), Medium-Low (17%-49%), Medium-High (50%-83%), and High (>83%).

(2) Nine evaluable sarcoma patients have received DeltaRex-G with an FDA approved drug (“DeltaRex-G Plus”) or as monotherapy between 2019 and 2024 (median OS = 7.4). Of these, four have known CCNG1 expression levels. Histological subtypes include Chondrosarcoma, Spindle cell sarcoma, Uterine Leiomyosarcoma, and Dedifferentiated Liposarcoma. Overall survival, duration of treatment, and responses (by RECIST v1.1 criteria) were evaluated.

Results: (1) All tumors showed enhanced CCNG1 expression. 38 (21%) tumors showed high CCNG1 expression, 62 (35%) had medium-high CCNG1 expression, 71 (40%) had medium-low CCNG1 expression, and 8 (4%) had low expression. 130 patients had metastatic disease and 49 had localized disease. There was no correlation between CCNG1 expression level and disease stage. Figure 1 presents the histological types tested. Figure 2 illustrates the CCNG1 expression level of each tumor sample tested.

(2) Of the four evaluable sarcoma patients with known CCNG1 levels who received DeltaRex-G, three are currently receiving treatment. All three patients had previously progressed with standard doses of chemotherapy. All patients are alive from 7.4 to 9.1 months since treatment initiation. Figure 3 illustrates the cancer type/CCNG1 expression level on the vertical axis and duration of survival, treatment duration, and responses on the horizontal axis. The fourth patient with chondrosarcoma, with a CCNG1 level of 74%, had an overall survival of 36.94 months. No serious treatment-related adverse events have been reported.

Conclusion: Taken together, the data demonstrates that (1) 100% of 179 tumors tested have enhanced CCNG1 expression, supporting the use of DeltaRex-G CCNG1 inhibitor therapy, (2) DeltaRex-G may evoke tumor growth stabilization in patients who previously failed standard chemotherapy, and (3) may prime tumors to better respond to chemotherapy, targeted therapy, and immunotherapy. Prospective studies are planned to correlate CCNG1 expression level with response to DeltaRex-G therapy.