- •Intraperitoneal Olvi-Vec was well tolerated in this phase 1 study of platinum-resistant/refractory ovarian cancer.
- •Nausea, fever, and abdominal distension were the most common treatment-related adverse events.
- •The ORR with monotherapy Olvi-Vec was 9%, stable disease ≥15 weeks was 46%, median PFS was 15.7 (95% CI: 5.7–34.5) weeks.
- •Three patients had extended overall survival (33.6 to 59+ months) following additional cytotoxic therapies.
- •Virus-induced tumor-specific T-cell activation in blood and CD8+ T-cell infiltration into tumor tissue were demonstrated.
Our objective was to assess safety and adverse events associated with intraperitoneal Olvi-Vec virotherapy in patients with platinum-resistant or refractory ovarian cancer (PRROC). Secondary objectives included objective response rate (ORR) per RECIST 1.1 and progression-free survival (PFS).
Olvi-Vec is a modified vaccinia virus that causes oncolysis and immune activation. An open-label phase 1b trial using a 3 + 3 dose escalation was conducted. Intraperitoneal Olvi-Vec was given as monotherapy in two consecutive daily doses. Translational analyses included anti-virus antibody levels, viral shedding, circulating tumor cells (CTCs) and T cells.
Twelve patients (median age: 69 years, range: 45–77) with median 5 prior therapies (range: 2–10) and 2 prior platinum lines (range: 1–5) were enrolled. There were three dose level cohorts: 3 × 109 (n = 6), 1 × 1010 (n = 5), and 2.5 × 1010 (n = 1) plaque forming units (PFU)/day on two consecutive days. Treatment-related adverse events (TRAEs) included G1/G2 nausea (n = 6), fever (n = 6), abdominal distention (n = 5), and abdominal pain (n = 4). There were no Grade 4 TRAEs, no dose relationship to TRAEs, and no deaths attributed to Olvi-Vec. The ORR was 9% (1/11). Stable disease (SD) was 64% (7/11), and SD ≥15 weeks was 46% (5/11). Median PFS was 15.7 weeks (95%CI: 5.7–34.5), including extended PFS in four patients (23.2, 34.5, 59.4+ and 70.8 weeks). Three patients had extended overall survival (deceased 33.6 months, and alive with disease at 54 and 59 months). CTCs diminished in 6/8 (75%) baseline-positive patients. Immune activation was demonstrated from virus-enhanced tumor infiltration of CD8+ T-cells and activation of tumor-specific T-cells in peripheral blood.
Oncolytic viral therapy with intraperitoneal Olvi-Vec showed promising safety, clinical activities, and immune activation in patients with PRROC, warranting further clinical investigation.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Gynecologic Oncology
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus.Cancer Res. 2007; 67: 10038-10046
- Permissivity of the NCI-60 cancer cell lines to oncolytic vaccinia virus GLV-1h68.BMC Cancer. 2011; 11: 451https://doi.org/10.1186/1471-2407-11-451
- The immunologic aspects of poxvirus oncolytic therapy.Cancer Immunol. Immunother. 2009; 58: 1355-1362
- Colonization of xenograft tumors by oncolytic vaccinia virus (VACV) results in enhanced tumor killing due to the involvement of myeloid cells.J. Transl. Med. 2016; 14: 340https://doi.org/10.1186/s12967-016-1096-1
- Phase I clinical trial of a genetically modified and oncolytic vaccinia virus GL-ONC1 with green fluorescent protein imaging (NCT009794131).J. Clin. Oncol. 2013; 31: 3062
- Phase I trial of intravenous oncolytic vaccinia virus (Olvi-Vec) with cisplatin and radiotherapy in patients with locoregionally advanced head and neck carcinoma.Clin. Cancer Res. 2017; 23: 5696-5702
- Phase I study of oncolytic vaccinia virus GL-ONC1 in patients with peritoneal carcinomatosis.Clin. Cancer Res. 2018; 15: 4388-4398
- Oncolytic virotherapy of gynecologic malignancies.Gynecol. Oncol. 2011; 120: 302-310
- Oncolytic viruses to treat ovarian cancer patients - a review of results from clinical trials.Geburtshilfe Frauenheilkd. 2012; 72: 132-136
- Chemotherapy enhances CD8(+) T cell-mediated antitumor immunity induced by vaccination with vaccinia virus.Mol. Ther. 2007; 15: 1558-1563
- Bugs and drugs: oncolytic virotherapy in combination with chemotherapy.Curr. Pharm. Biotechnol. 2012; 13: 1817-1833
- Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial.Lancet Oncol. 2019; 20: 636-648
- Maintenance of the nutritional prognostic index predicts survival in patients with unresectable metastatic colorectal cancer.J. Cancer Res. Clin. Oncol. 2015; 141: 307-313
- Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis.Cancer Treat. Res. 1996; 82: 359-374
- Circulating tumor cells and colorectal cancer.Curr. Colorectal Cancer Rep. 2010; 6: 212-220
- Immunologic monitoring of cancer vaccine trials using the ELISPOT assay.Meth. Mol. Biol. 2014; 1102: 71-82
- Bevacizumab combined with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan in platinum-resistant recurrent ovarian cancer: analysis by chemotherapy cohort of the randomized phase III AURELIA trial.J. Clin. Oncol. 2015; 33: 3836-3838
- Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study.Ann. Oncol. 2019; 30: 1080-1087
- Heating it up: oncolytic viruses make tumors ‘hot’ and suitable for checkpoint blockade immunotherapies.Oncoimmunology. 2018; 7e1442169
- Visualization of tumors and metastases in live animals with bacteria and vaccinia virus encoding light-emitting proteins.Nat. Biotechnol. 2004; 22: 313-320
- The highly attenuated oncolytic recombinant vaccinia virus GLV-1h68: comparative genomic features and the contribution of F14.5L inactivation.Mol. Genet. Genomics. 2009; 282: 417-435
- The formation and function of extracellular enveloped vaccinia virus.J. Gen. Virol. 2002; 83: 2915-2931
- Smallpox vaccines: past, present, and future.J. Allergy Clin. Immunol. 2006; 118: 1320-1326
- Modified vaccinia virus Ankara exerts potent immune modulatory activities in a murine model.PLoS One. 2010; 5e11400
- Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination.Nat. Commun. 2021; 12: 2626https://doi.org/10.1038/s41467-021-22929-z
- Immune modulation by chemotherapy or immunotherapy to enhance cancer vaccines.Cancers (Basel). 2011; 3: 3114-3142
- The interplay of immunotherapy and chemotherapy: harnessing potential synergies.Cancer Immunol. Res. 2015; 3: 436-443
- Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1.Gene Ther. 2011; 18: 164-172
- cGAS-STING and Cancer: dichotomous roles in tumor immunity and development.Trends Immunol. 2018; 39: 44-54
- Effector T-cells abrogate stroma-mediated chemoresistance in ovarian cancer.Cell. 2016; 165: 1092-1105
- Immune effects of bevacizumab: killing two birds with one stone.Cancer Microenviron. 2015; 8: 15-21
- Oncolytic vaccinia (Olvi-Vec) primed immunochemotherapy in platinum-resistant/ refractory ovarian cancer.Int. J. Gynecol. Cancer. 2020; 30: A9-A10
- Phase II trial of oncolytic vaccinia virus primed immunochemotherapy in platinum-resistant/refractory ovarian cancer (PRROC) (NCT02759588). E-Poster Presentation at the European Society for Medical Oncology (ESMO) Congress, September 18–22, 2020, Madrid, Spain.Ann. Oncol. 2020; 31: S628
Published online: October 19, 2021
Accepted: October 10, 2021
Received in revised form: October 1, 2021
Received: August 25, 2021
© 2021 Elsevier Inc. All rights reserved.