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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.
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DNG64-CAR-V | Drug | 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. |
|
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| ERLINDA M GORDON, MD | Contact | 3105529999 | egordon@sarcomaoncology.com | |
| Victoria Chua-Alcala, MD | Contact | 3105529999 | vchua@sarcomaoncology.com |
| Name | Affiliation | Role |
|---|---|---|
| ERLINDA M GORDON, MD | Sarcoma Oncology Research Center, LLC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sarcoma Oncology Research Center, LLC | Available | Santa Monica | California | 90403 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28588778 | Background | Kim S, Federman N, Gordon EM, Hall FL, Chawla SP. Rexin-G(R), a tumor-targeted retrovector for malignant peripheral nerve sheath tumor: A case report. Mol Clin Oncol. 2017 Jun;6(6):861-865. doi: 10.3892/mco.2017.1231. Epub 2017 Apr 28. | |
| Background | Chawla SP, Chawla NS, Quon D, Chua-Alcala V, Blackwelder WC, Hall FL and Gordon EM: An advanced phase 1/2 study using an XC-targeted gene therapy vector for chemotherapy resistant sarcoma. Sarcoma Res Int 3: 1024, 2016 | ||
| 20384524 |
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| Background |
| Gordon EM, Hall FL. Rexin-G, a targeted genetic medicine for cancer. Expert Opin Biol Ther. 2010 May;10(5):819-32. doi: 10.1517/14712598.2010.481666. |
| 19532136 | Background | Chawla SP, Chua VS, Fernandez L, Quon D, Saralou A, Blackwelder WC, Hall FL, Gordon EM. Phase I/II and phase II studies of targeted gene delivery in vivo: intravenous Rexin-G for chemotherapy-resistant sarcoma and osteosarcoma. Mol Ther. 2009 Sep;17(9):1651-7. doi: 10.1038/mt.2009.126. Epub 2009 Jun 16. |
| 30705966 | Background | Chawla SP, Bruckner H, Morse MA, Assudani N, Hall FL, Gordon EM. A Phase I-II Study Using Rexin-G Tumor-Targeted Retrovector Encoding a Dominant-Negative Cyclin G1 Inhibitor for Advanced Pancreatic Cancer. Mol Ther Oncolytics. 2018 Dec 14;12:56-67. doi: 10.1016/j.omto.2018.12.005. eCollection 2019 Mar 29. |
| 30581985 | Background | Al-Shihabi A, Chawla SP, Hall FL, Gordon EM. Exploiting Oncogenic Drivers along the CCNG1 Pathway for Cancer Therapy and Gene Therapy. Mol Ther Oncolytics. 2018 Dec 12;11:122-126. doi: 10.1016/j.omto.2018.11.002. eCollection 2018 Dec 21. No abstract available. |
| 39086675 | Background | Bruckner HW, Chawla SP, Omelchenko N, Brigham DA, Gordon EM. Phase I-II study using DeltaRex-G, a tumor-targeted retrovector encoding a cyclin G1 inhibitor for metastatic carcinoma of breast. Front Mol Med. 2023 May 18;3:1105680. doi: 10.3389/fmmed.2023.1105680. eCollection 2023. |
| 37247916 | Background | Chawla SP, Olevsky O, Iyengar G, Brigham DA, Omelchenko N, Thomas S, Suryamohan K, Foshag L, Hall FL, Gordon EM. Early-stage CCNG1+ HR+ HER2+ Invasive Breast Carcinoma in Older Women: Current Treatment and Future Perspectives for DeltaRex-G, a CCNG1 Inhibitor. Anticancer Res. 2023 Jun;43(6):2383-2391. doi: 10.21873/anticanres.16406. |
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| D012516 | Osteosarcoma |
| D018319 | Neurofibrosarcoma |
| D002813 | Chondrosarcoma |
| D012509 | Sarcoma |
| D002817 | Chordoma |
| D001943 | Breast Neoplasms |
| D010051 | Ovarian Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D018213 | Neoplasms, Bone Tissue |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D005354 | Fibrosarcoma |
| D018218 | Neoplasms, Fibrous Tissue |
| D009455 | Neurofibroma |
| D018317 | Nerve Sheath Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D010524 | Peripheral Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009422 | Nervous System Diseases |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D005834 | Genital Neoplasms, Male |
| D005832 | Genital Diseases, Male |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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