GL-ONC1

GL-ONC1 (USAN: olvimulogene nanivacirepvec; abbreviated as Olvi-Vec) is an investigational therapeutic product consisting of the clinical grade formulation of the laboratory strain GLV-1h68, an oncolytic virus developed by Genelux Corporation.[1] GL-ONC1 is currently under evaluation in Phase I/II human clinical trials in the United States and Europe.[2]

GL-ONC1 (CAS Registry Number (CAS RN): 1473430-36-2) is a triple modified and attenuated vaccinia virus (Lister strain) that causes regression and elimination of a wide range of solid tumors in preclinical mouse models.[3] It was generated by insertion of three expression cassettes (encoding Renilla luciferase-Aequorea green fluorescent protein fusion, beta-galactosidase, and beta-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase) and A56R (encoding hemagglutinin) loci of the parental viral Lister strain genome, respectively.[1] The oncolytic virus specifically infects and kills tumor cells which leads to oncolysis, immune activation and triggering anti-tumor immune responses.[4][5][6]

Clinical trials

Regional (cavity) administration

One Phase I/II Study of intraperitoneal administration of GL-ONC1 in patients with advanced peritoneal carcinomatosis has been completed.[7][8] A Phase II study of intraperitoneal administration of GL-ONC1 (Olvi-Vec) in heavily-pretreated patients with platinum-resistant/refractory ovarian cancer was completed.[9][10] Positive clinical data have been reported in IGCS 2020 and ESMO 2020 conferences. [11] [12] A registration trial of Olvi-Vec(aka GL-ONC1)-primed immunochemotherapy is being planned.

In a Phase I study, intra-pleural administration of GL-ONC1 is being evaluated in patients with malignant pleural effusion, which is caused by cancer from malignant pleural mesothelioma, non-small cell lung cancer (NSCLC), or breast cancer.[13] In this trial GL-ONC1 infection of tumor cells was identified in 6 out of 8 patients with epithelioid malignant pleural mesothelioma.[14]

Systemic (intravenous) administration

Systemic administration of GL-ONC1 via intravenous injection was under investigation in multiple clinical trials:

In one study, GL-ONC1 was administered to patients with advanced solid organ tumors as a monotherapy.[15] In another completed study, GL-ONC1 was given in combination with radiation therapy and cisplatin (CDDP) to patients with locoregionally advanced head and neck cancer.[16][17]

References
  1. Zhang Q, Yu YA, Wang E, Chen N, Danner RL, Munson PJ, Marincola FM, Szalay AA (October 2007). "Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus". Cancer Research. 67 (20): 10038–46. doi:10.1158/0008-5472.can-07-0146. PMID 17942938.
  2. "Search of: GL-ONC1 - List Results - ClinicalTrials.gov". clinicaltrials.gov.
  3. Donat U, Weibel S, Hess M, Stritzker J, Härtl B, Sturm JB, Chen NG, Gentschev I, Szalay AA (2012). "Preferential colonization of metastases by oncolytic vaccinia virus strain GLV-1h68 in a human PC-3 prostate cancer model in nude mice". PLOS One. 7 (9): e45942. doi:10.1371/journal.pone.0045942. PMC 3457966. PMID 23049897.
  4. Melcher A, Parato K, Rooney CM, Bell JC (June 2011). "Thunder and lightning: immunotherapy and oncolytic viruses collide". Molecular Therapy. 19 (6): 1008–16. doi:10.1038/mt.2011.65. PMC 3129809. PMID 21505424.
  5. Tong AW, Senzer N, Cerullo V, Templeton NS, Hemminki A, Nemunaitis J (July 2012). "Oncolytic viruses for induction of anti-tumor immunity". Current Pharmaceutical Biotechnology. 13 (9): 1750–60. doi:10.2174/138920112800958913. PMID 21740355.
  6. Naik JD, Twelves CJ, Selby PJ, Vile RG, Chester JD (July 2011). "Immune recruitment and therapeutic synergy: keys to optimizing oncolytic viral therapy?". Clinical Cancer Research. 17 (13): 4214–24. doi:10.1158/1078-0432.ccr-10-2848. PMC 3131422. PMID 21576084.
  7. Clinical trial number NCT01443260 for "A Study of GL-ONC1, an Oncolytic Vaccinia Virus, in Patients With Advanced Peritoneal Carcinomatosis" at ClinicalTrials.gov
  8. Lauer UM, Schell M, Beil J, Berchtold S, Koppenhöfer U, Glatzle J, et al. (May 2018). "Phase I study of oncolytic vaccinia virus GL-ONC1 in patients with peritoneal carcinomatosis". Clinical Cancer Research. doi:10.1158/1078-0432.CCR-18-0244. PMID 29773661.
  9. Clinical trial number NCT02759588 for "GL-ONC1 Oncolytic Immunotherapy in Patients With Recurrent Ovarian Cancer" at ClinicalTrials.gov
  10. Holloway RW et al. (March 2020) "Phase II VIRO-15 trial of olvimulogene nanivacirepvec (Olvi-Vec)-primed immunochemotherapy in platinum-resistant/refractory ovarian cancer (PRROC) (NCT02759588)".
  11. Holloway RW et al. (September 2020) "Genelux Announces Oral Plenary Presentation of VIRO-15 Phase 2 Trial Data at the 2020 xDigital Annual Global Meeting of the International Gynecologic Cancer Society".
  12. Holloway RW et al. (September 2020) "Genelux to Present Data from Phase 2 Trial of Olvi-Vec in Heavily Pre-treated Platinum-Resistant/Refractory Ovarian Cancer at ESMO Virtual Congress 2020".
  13. Clinical trial number NCT01766739 for "Intra-pleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma" at ClinicalTrials.gov
  14. Krug LM, Zauderer MG, Adusumili PS, McGee E, Sepkowitz K, Klang M, et al. (May 2015). "Phase I study of intra-pleural administration of GL-ONC1, an oncolytic vaccinia virus, in patients with malignant pleural effusion". Journal of Clinical Oncology. 33 (15_suppl): 7559–7559. doi:10.1200/jco.2015.33.15_suppl.7559.
  15. Clinical trial number NCT00794131 for "Safety Study of GL-ONC1, an Oncolytic Virus, in Patients With Advanced Solid Tumors" at ClinicalTrials.gov
  16. Clinical trial number NCT01584284 for "Safety Study of Attenuated Vaccinia Virus (GL-ONC1) With Combination Therapy in Head & Neck Cancer" at ClinicalTrials.gov
  17. Mell LK et al. (July 2017) "Phase I Trial of Intravenous Oncolytic Vaccinia Virus (GL-ONC1) with Cisplatin and Radiotherapy in Patients with Locoregionally Advanced Head and Neck Carcinoma" (PDF).
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