However, in the ensuing years, drug development of the tumor-targeted gene therapy seemed to stop, and this pause continued for nearly the next decade. Howard W. Bruckner, MD, Bruckner Oncology, The Bronx, New York, has been involved in the research, including that reported at ASGCT, and told Cancer Therapy Advisor that the hiatus in work on the drug was due to “purely money.” He said there was no financing to continue making the product or to fund trials. “Very disappointing, everything considered,” he added.

Dr Gordon, director of biological and immunological therapies at the Cancer Center of Southern California, Santa Monica, explained to Cancer Therapy Advisor that Epeius Biotechnologies was “taken over by controlling interest in late 2010, and for undisclosed reasons, the new management decided not to develop Rexin-G.” She noted that Dr Hall and she had left the company by that point, and in May 2018, Dr Gordon founded the Aveni Foundation, a nonprofit organization that she said has undertaken the task of making DeltaRex-G and DeltaVax available to patients.

The majority of chemotherapy-resistant patients with metastatic disease who were treated with DeltaRex-G (with or without DeltaVax) that were enrolled in clinical trials have died, but 8 patients remain alive more than 10 years later. Patients received a median of 50 infusions for DeltaRex-G and 6 infusions for DeltaVax over 6 months. The number of infusions administered to each patient was dependent, in part, on the patient’s willingness to receive additional infusions and also their positron emission tomography scan results. For example, 1 patient still alive at the 10-year follow-up received 205 infusions of DeltaRex-G.

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Of the 8 living patients, 5 received DeltaRex-G alone. These 5 patients include 1 person with metastatic pancreatic adenocarcinoma, 2 people with metastatic osteosarcomas, 1 person with malignant peripheral nerve sheath tumor, and 1 person with ductal carcinoma in situ (DCIS) that metastasized to bone. The remaining 3 living patients received DeltaRex-G in combination with DeltaVax; these 3 patients include 1 individual with B-cell lymphoma that metastasized to the liver and pancreas, 1 individual with locally advanced chondroblastic osteosarcoma of maxilla, and 1 individual with DCIS that metastasized to bone. 

Seven of the 8 living patients had no evidence of disease at follow-up; the patient with DCIS had disease progression and was on capecitabine for liver metastasis. Long-term responses were attributed to DeltaRex-G (with or without DeltaVax) because the 7 patients with no evidence of disease did not receive any additional cancer therapy. 

When asked whether these outliers had any unique tumor characteristics that could help explain their responses, Dr Bruckner said that at the time of these trials, “The technology for genomics and proteomics was comparatively in its infancy.” 

“Now we’ve got the impetus to do that,” Dr Bruckner said. Phase 2 clinical trials for sarcoma, pancreatic cancer, and glioblastoma are currently being planned. He added, “This time we will have some prospective plans for serial biopsies to get a better look at genomic and proteomic changes [and] the current immunologic biomarkers of interest.”

References

  1. Bruckner H, Chawla SP, Liu SY, et al. Phase I-II study using Rexin-G, a tumor-targeted retrovector encoding a cyclin G1 inhibitor for metastatic carcinoma of breast: A ten-year follow-up. Poster presented at: 2019 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting; Washington, D.C.; April 29-May 2, 2019. Abstract 273. 
  2. Liu SY, Chawla SP, Bruckner H, et al. Reporting long term survival following precision tumor-targeted gene delivery to advanced chemotherapy-resistant malignancies: An academic milestone. Poster presented at: 2019 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting; Washington, D.C.; April 29-May 2, 2019. Abstract 275.
  3. Gordon EM, Hall FL. Rexin-G, a targeted genetic medicine for cancer. Expert Opin Biol Ther. 2010;10(5):819-832.