**3.2 A Phase I-II Study Using DeltaRex-G (Former name:Rexin-G)Tumor-Targeted Retrovector Encoding a Dominant-Negative Cyclin G1 Inhibitor for Advanced Pancreatic Cancer (NCT00504998) Sant P. Chawla, Michael Morse, Howard Bruckner, Principal Investigators**

### *3.2.1 Background & rationale*

Advanced pancreatic adenocarcinoma is the third most common cancer type in the Unites States, although diagnostic tests are non-specific which leads to early-stage disease frequently going undetected [49, 50]. Once pancreatic adenocarcinoma reaches an advanced stage, it has likely become intractable and there is no cure. Previous targeted therapies revolved around the epidermal growth factor receptor (EGFR) signaling pathway, one of the most significant factors regulating cell growth, survival, differentiation and proliferation, making it a promising target for precision medicine [51]. EGFR signaling has been identified as an oncogenic driver in multiple cancer types, and EGFR inhibitors have been used as targeted therapy for pancreatic cancer [52].

DeltaRex-G is the first injectable tumor-targeted gene delivery system to be developed for cancer that blocks the G1 checkpoint of the cell division cycle of cancer cells by inhibiting the CCNG1 gene. DeltaRex-G includes a mutant construct of the CCNG1 gene that inhibits human cyclin G1, a proto-oncogene that promotes cell competence, cell survival, and stem cell proliferation. When administered systemically, DeltaRex-G seeks out and accumulates in tumor tissues by binding abnormal collagenous signature (SIG) proteins that are characteristically exposed as anaplasia during tumor invasion. Once the DeltaRex-G retrovector is incorporated in rapidly dividing cells, a cytocidal CCNG1 inhibitor protein is expressed that effectively blocks the cell division cycle, resulting in apoptosis and subsequent eradication of cancer cells, proliferative vasculature, and stroma.

Clinical data from DeltaRex-G trials conducted initially in the Philippines showed promising results for patients with advanced pancreatic adenocarcinoma. This prompted USFDA Orphan Drug status, leading to progressive clinical trials in the United States, using DeltaRex-G to treat chemotherapy-resistant advanced pancreatic adenocarcinoma, soft tissue sarcoma, osteosarcoma, and breast cancers. This study reports the results compiled from a Phase I-II clinical trial using intravenous infusions of DeltaRex-G as treatment for advanced pancreatic cancer.
