Carcinoma of Breast, Chondrosarcoma, Chordoma, MPNST (Malignant Peripheral Nerve Sheath Tumor), Osteosarcoma, Pancreatic Cancer, Sarcoma, Single Patient IND for Glioblastoma, Ovarian Carcinoma, Non-small Cell Lung Cancer , Prostate Cancer, Soft Tissue Sarcoma
Conditions
Keywords
tumor targeted gene therapy, human cyclin G1 inhibitor, cell cycle control, CCNG1 inhibitor
Brief summary
Forty patients with pancreatic cancer, sarcoma and carcinoma of breast will receive DNG64-CAR-V intravenously or intratumorally at a dose of 1-4 x 10e11 colony forming units (cfu) or equivalent 1.0-6.0 x 10e10 Vector Copies (VC) per dose one to three times a week. DNG64-CAR-V may be given alone or with one or more FDA approved cancer therapies/immunotherapies, or with certain FDA authorized investigational agents. Based on previous Phase 1/2 US based clinical studies, DNG64-CAR-V does not suppress the bone marrow or cause organ dysfunction, and enhanced immune cell trafficking in tumors may cause the tumors to appear larger or new lesions to appear on CT, PET or MRI (pseudoprogression). Further, tumor stabilization/regression/remission have occurred later during the treatment period with DNG64-CAR-V monotherapy. Therefore, DNG64 -CAR-V will be continued if the patient has clinical benefit and does not have symptomatic disease progression.
Detailed description
DNG64-CAR-V is a replication incompetent chimeric tumor targeted amphtropic RNA vector that displays a Sig-binding decapeptide for binding to abnormally exposed Signature (Sig) proteins in the tumor microenvironment (TME) and encoding a CCNG1 inhibitor gene for killing cancer cells, neoangiogenic cells and pro-inflammatory, immune suppressive, stroma producing cancer associated fibroblasts (CAFs), thus reducing inflammation and converting an immune-cold to an immune-hot tumor, and reducing extracellular matrix production in the TME, hence augmenting drug entry and immune cell trafficking into the TME. Enhanced CCNG1 expression has been found in all cancer types tested at the Cancer Center of Southern California as of June 2023. Hence, in July 2023, the USFDA authorized the use of DNG64-CAR-V as platform therapy upon which one or more FDA approved cancer drugs immunotherapies and/or certain FDA authorized investigational agents may be added. This would allow a personalized approach in the treatment of all cancer patients. Forty patients with pancreatic cancer, sarcoma and carcinoma of breast will receive DNG64-CAR-V intravenously or intratumorally at a dose of 1-4 x 10e11 colony forming units (cfu) or equivalent 1.0-6.0 x 10e10 VC per dose one-three times a week. DNG64-CAR-V may be given alone or with an FDA approved cancer therapy/immunotherapy and/or certain FDA authorized investigational agents on physician discretion.
Interventions
DRUGDNG64-CAR-V
Intravenous or intratumoral infusions of DNG64-CAR-V for treatment of advanced pancreatic cancer, sarcoma and carcinoma of breast and other FDA authorized cancer types.
Sponsors
Aveni Foundation
Eligibility
Sex/Gender
ALL
Age
12 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Patient is ≥12 years of age, either male or female for patients with sarcoma; \>18 years of age, either male or female.with pancreatic cancer or carcinoma of breast. * Patient has pancreatic cancer or sarcoma or carcinoma of breast confirmed by pathologic examination at diagnosis. * Patients with advanced metastatic pancreatic cancer who have received systemic therapies such as FOLFIRINOX and gemcitabine + albumin-bound paclitaxel; patients with metastatic sarcoma who have disease progression after two or more lines of systemic treatments and not amenable to surgical resection or radiotherapy; specifically for osteosarcoma: have disease progression after high dose methotrexate, cisplatinum, doxorubicin and ifosfamide; for soft tissue sarcoma: have disease progression after doxorubicin + ifosfamide/mesna, gemcitabine, docetaxel, dacarbazine, trabectedin, pazopanib, eribulin; patients with metastatic carcinoma of breast who have disease progression with standard therapy (ACT), targeted therapies including aromatase inhibitors, trastuzumab, pertuzumab, enhertu, tyrosine kinase inhibitors, immune checkpoint inhibitors; patient who is intolerant to or declines available therapeutic options after documentation that patient has been informed of the available therapeutic options. * Patient is able to understand or is willing to sign a written informed consent. * Patient agrees to use barrier contraception during vector infusion period and for 6 weeks after infusion
Exclusion criteria
* Patient is unwilling to provide formal informed consent. * Patient is unwilling to use barrier contraception during vector infusion period and for 6 weeks after infusion
Countries
United States
Contacts
CONTACTERLINDA M GORDON, MD
CONTACTVictoria Chua-Alcala, MD
PRINCIPAL_INVESTIGATORERLINDA M GORDON, MD
Sarcoma Oncology Research Center, LLC
Outcome results
None listed