Phase I-II study using DeltaRex-G, a tumor-targeted retrovector encoding a cyclin G1 inhibitor for metastatic carcinoma of breast.

Metastatic breast cancer is associated with a poor prognosis and therefore, innovative therapies are urgently needed. Here, we report on the results of a Phase I-II study using DeltaRex-G for chemotherapy resistant metastatic carcinoma of breast. Dose limiting toxicity; Antitumor activity. : ≥18 years of age, pathologic diagnosis of breast carcinoma, adequate hematologic and organ function. : Dose escalation of DeltaRex-G 1-4 x 10cfu intravenously thrice weekly x 4 weeks with 2-week rest period. Treatment cycles repeated if there is ≤ Grade 1 toxicity until disease progression or unacceptable toxicity. NCI CTCAE v3 for adverse events reporting, vector related testing. RECIST v1.0, International PET criteria and Choi criteria for response, progression free and overall survival. Twenty patients received escalating doses of DeltaRex-G from 1 × 10 cfu to 4 × 10 cfu thrice weekly for 4 weeks with a 2-week rest period. : ≥ Grade 3 treatment-related adverse event: pruritic rash ( = 1), no dose limiting toxicity, no replication-competent retrovirus, nor vector-neutralizing antibodies detected. No vector DNA integration was observed in peripheral blood lymphocytes evaluated. : by RECIST v1.0: 13 stable disease, 4 progressive disease; tumor control rate 76%; by PET and Choi Criteria: 3 partial responses, 11 stable disease, 3 progressive disease; tumor control rate 82%. Combined median progression free survival by RECIST v1.0, 3.0 months; combined median overall survival, 20 months; 1-year overall survival rate 83% for Dose Level IV. Biopsy of residual tumor in a participant showed abundant CD8 killer T-cells and CD45 macrophages suggesting an innate immune response. Two patients with pure bone metastases had >12-month progression free survival and overall survival and are alive 12 years from the start of DeltaRex-G therapy. These patients further received DeltaRex-G + DeltaVax for 6 months. Taken together, these data indicate that 1) DeltaRex-G has a distinctively high level of safety and exhibits anti-cancer activity, 2) PET/Choi provide a higher level of sensitivity in detecting early signs of tumor response to DeltaRex-G, 3) DeltaRex-G induced 12- year survival in 2 patients with pure bone metastases who subsequently received DeltaVax immunotherapy, and 4) DeltaRex-G may prove to be a biochemical and/or immune modulator when combined with other cancer therapy/immunotherapy.