Seiya Liu1,2, Sant P Chawla3, Howard Bruckner4, Michael A Morse5, Noah Federman6, Amor Srikureja3, Don A Brigham3, Jorge G Ignacio7, Filomena San Juan8, Roseo A Manalo9 and Erlinda M Gordon3,9,10*
1Harvard University, USA
2University of Miami Miller School of Medicine, USA
3Sarcoma Oncology Center/Cancer Center of Southern California, USA
4Bruckner Oncology, USA
5Duke University Medical Center, USA
6David Geffen UCLA Medical Center, USA
7Philippine General Hospital, Philippines
8University of the Philippines, Philippines
9University of Santo Tomas College of Medicine and Surgery, Philippines
10Aveni Foundation, USA
Background and Purpose: DeltaRex-G is a tumor-targeted retrovector (1) displaying a Signature (SIG)-decapeptide for binding to anaplastic SIG proteins that are abnormally exposed in the tumor microenvironment, and (2) encoding a cytocidal CCNG1 inhibitor gene for killing rapidly dividing cells such as cancer cells. DeltaVax is a tumor-targeted retrovector encoding two genes, (1) a GMCSF gene for in situ autovaccination, and (2) the HSVtk gene for regulating GM-CSF expression in cancer cells. This case series reports on the long-term survival of patients who participated in five Phase 1/2 and Phase 2 US-based and one Phase 1/2 Philippine-based clinical trials using intravenous DeltaRex-G, with or without DeltaVax, for locally advanced or metastatic cancer.
Methods and Patients: The case report forms of patients enrolled in the above-mentioned FDA and IRB approved clinical trials were reviewed and survival data documented. Results: Ninety-eight patients with advanced chemo-resistant solid malignancies received >5,000 intravenous infusions of DeltaRex-G. Another 16 patients received 288 intravenous infusions of DeltaRex-G with 96 infusions of DeltaVax followed by valacyclovir orally. Cancer types include pancreatic adenocarcinoma (n=1), osteosarcoma (n=3), MPNST (n=1), invasive breast carcinoma (n=2), and B-cell lymphoma (n=1). The median estimated tumor burden was 29.1 × 109 (range: 6.2 tob75.5 × 109) cancer cells, median duration of treatment was 20 (range: 6 to 28) months, and median duration of survival was 12 (range: 10 to 12) years from DeltaRex-G treatment initiation. Survival analysis showed 5 of 98 (5.1%) 10 to 12-year survival rate for patients who received DeltaRex-G alone, 3 of 22 (13.6%) for osteosarcoma patients receiving DeltaRex-G alone, and 4 of 16 (25%) for
DeltaRex-G + DeltaVax combination.
Conclusion: Taken together, these data suggest that DeltaRex-G, with or without DeltaVax, may induce prolonged survival in advanced chemo-resistant solid malignancies and B-cell lymphoma. Points to consider going forward with the next phase 2 and phase 3 clinical trials using DeltaRex-G include patient's (1) estimated tumor burden (2) risk of recurrence/disease progression after standard therapy, (3) molecular profile of tumor, and (4) CCNG1 expression levels in tumors and circulating tumor cells, to identify patients who will benefit the most with DeltaRex-G/DeltaVax therapy.
Tumor-targeted cancer gene therapy; Cell cycle control; CCNG1; Metastatic cancer; Chemotherapy resistant cancer; Pancreatic cancer; Sarcoma; Osteosarcoma; Breast cancer; B-cell lymphoma
Liu S, Chawla SP, Bruckner H, Morse MA, Federman N, Srikureja A, et al. Long Term Survival Following DeltaRex-G/DeltaVax Tumor-Targeted Gene Therapy for Advanced Chemotherapy-Resistant Malignancies: An Academic Milestone. Clin Oncol.