12 Oncolytic vaccinia (Olvi-Vec) primed immunochemotherapy in platinum-resistant/refractory ovarian cancer

Holloway, R. W.; Mendivil, Alberto A.; Kendrick, James E.; Abaid, Lisa N.; Brown, John V.; Fitzsimmons, Christine; Kennard, Jessica A.; King, Monica M; LeBlanc, Jane; Lopez, Katrina L.; Manyam, Madhavi; McKenzie, Nathalie D.; Mori, Kristina M.; Stephens, Amanda J.; Ahmad, S

doi:10.1136/ijgc-2020-igcs.12

Cited by 4 publications

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“…Virus-mediated tumor cell lysis may induce immune priming by increasing T-cell response through cross-presentation of the tumor (neo)antigens, and being further boosted by subsequent cytotoxic chemotherapy . In this population, Olvi-Vec was associated with an influx of CD4-positive and CD8-positive tumor-infiltrating lymphocytes in paired tumor biopsy samples, which was a positive prognostic factor in patients with ovarian cancer . Overall, Olvi-Vec may convert immunologically “cold” to “hot” tumors by modifying the tumor microenvironment and abrogate platinum resistance …”

Section: Discussionmentioning

confidence: 97%

Clinical Activity of Olvimulogene Nanivacirepvec–Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer

et al. 2023

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ImportancePatients with platinum-resistant or platinum-refractory ovarian cancer (PRROC) have limited therapeutic options, representing a considerable unmet medical need.ObjectiveTo assess antitumor activity and safety of intraperitoneal (IP) olvimulogene nanivacirepvec (Olvi-Vec) virotherapy and platinum-based chemotherapy with or without bevacizumab in patients with PRROC.Design, Setting, and ParticipantsThis open-label, nonrandomized multisite phase 2 VIRO-15 clinical trial enrolled patients with PRROC with disease progression following their last prior line of therapy from September 2016 to September 2019. Data cutoff was on March 31, 2022, and data were analyzed between April 2022 and September 2022.InterventionsOlvi-Vec was administered via a temporary IP dialysis catheter as 2 consecutive daily doses (3 × 109 pfu/d) followed by platinum-doublet chemotherapy with or without bevacizumab.Main Outcomes and MeasuresPrimary outcomes were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) and cancer antigen 125 (CA-125) assay, and progression-free survival (PFS). Secondary outcomes included duration of response (DOR), disease control rate (DCR), safety, and overall survival (OS).ResultsTwenty-seven heavily pretreated patients with platinum-resistant (n = 14) or platinum-refractory (n = 13) ovarian cancer were enrolled. The median (range) age was 62 (35-78) years. The median (range) prior lines of therapy were 4 (2-9). All patients completed both Olvi-Vec infusions and chemotherapy. Median follow-up duration was 47.0 months (95% CI, 35.9 months to NA). Overall, ORR by RECIST 1.1 was 54% (95% CI, 33%-74%), with a DOR of 7.6 months (95% CI, 3.7-9.6 months). The DCR was 88% (21/24). The ORR by CA-125 was 85% (95% CI, 65%-96%). Median PFS by RECIST 1.1 was 11.0 months (95% CI, 6.7-13.0 months), and the PFS 6-month rate was 77%. Median PFS was 10.0 months (95% CI, 6.4-NA months) in the platinum-resistant group and 11.4 months (95% CI, 4.3-13.2 months) in the platinum-refractory group. The median OS was 15.7 months (95% CI, 12.3-23.8 months) in all patients, with a median OS of 18.5 months (95% CI, 11.3-23.8 months) in the platinum-resistant group and 14.7 months (95% CI, 10.8-33.6 months) in the platinum-refractory group. Most frequent treatment-related adverse events (TRAEs) (any grade, grade 3) were pyrexia (63.0%, 3.7%, respectively) and abdominal pain (51.9%, 7.4%, respectively). There were no grade 4 TRAEs, and no treatment-related discontinuations or deaths.Conclusions and RelevanceIn this phase 2 nonrandomized clinical trial, Olvi-Vec followed by platinum-based chemotherapy with or without bevacizumab as immunochemotherapy demonstrated promising ORR and PFS with a manageable safety profile in patients with PRROC. These hypothesis-generating results warrant further evaluation in a confirmatory phase 3 trial.Trial RegistrationClinicalTrials.gov Identifier: NCT02759588

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Section: Discussionmentioning

confidence: 97%

Clinical Activity of Olvimulogene Nanivacirepvec–Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer

et al. 2023

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“…The median PFS was 11.0 months (95% CI: 6.7–13.0), and the PFS-6-month was 77%. Thus, the majority of patients achieved RECIST response with a median PFS exceeding their prior line of therapy [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model

Koch

Beil

Berchtold

et al. 2023

Viruses

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Oncolytic virotherapy constitutes a promising treatment option for many solid cancers, including peritoneal carcinomatosis (PC), which still represents a terminal stage of many types of tumors. To date, the in vitro efficacy of oncolytic viruses is mostly tested in 2D-cultured tumor cell lines due to the lack of realistic 3D in vitro tumor models. We have investigated the feasibility of virotherapy as a treatment option for PC in a human ex vivo peritoneum co-culture model. Human HT-29 cancer cells stably expressing marker genes GFP and firefly luciferase (GFP/luc) were cultured on human peritoneum and infected with two prototypic oncolytic viruses (GLV-0b347 and MeV-DsRed). Both viral constructs were able to infect HT-29 cells in patient-derived peritoneum with high tumor specificity. Over time, both GFP signal and luciferase activity decreased substantially, thereby indicating successful virus-induced oncolysis. Furthermore, immunohistochemistry stainings showed specific virotherapeutic infections of HT-29 cells and effective tumor cell lysis in infected co-cultures. Thus, the PC model established here provides a clinically relevant screening platform to evaluate the therapeutic efficacy of virotherapeutic compounds and also to investigate, in an autologous setting, the immunostimulatory potential of oncolytic viruses for PC in a unique human model system superior to standard 2D in vitro models.

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“… 42 A multi-center phase II trial of Olvi-Vec followed by platinum-doublet therapy with or without bevacizumab has since been completed and presented at IGCS 2020 and ESMO 2020 conferences. 43 , 44 Furthermore, a multi-institutional randomized phase III trial in PRROC with Olvi-Vec is currently underway [NCT05281471].…”

Section: Other Categories Of Emerging Immunotherapymentioning

confidence: 99%

Immunotherapy in the Treatment of Platinum-Resistant Ovarian Cancer: Current Perspectives

Awada¹,

Ahmad²,

McKenzie³

et al. 2022

OTT

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Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The gold standard therapeutic approach is a combination of surgery plus chemotherapy. Unfortunately, 80% of patients with EOC suffer recurrence within 2-years and the overall response rate for platinum-resistant epithelial ovarian cancer to cytotoxic chemotherapy or poly-(adenosine diphosphate)-ribose polymerase (PARP) inhibitor is modest. New therapies are needed to improve overall survival. The role of immunotherapy has been established in endometrial and cervical cancers, however its effective use in EOC has been limited due to the intrinsic genomics and micro-immune environment associated with EOC. Studies evaluating immunotherapy, largely immune checkpoint inhibitors (ICI), have shown limited activity, yet some patients benefit greatly. Thus, significant efforts must be devoted to finding new strategies for the use of immunotherapy/immunomodulatory drugs (IMiDs). Immunotherapy has a well-tolerated safety profile; however, cost-effectiveness can be an obstacle. The aim of this article is to review the most recent research into the use of IMiDs in patients with platinum-resistant epithelial ovarian cancer.

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12 Oncolytic vaccinia (Olvi-Vec) primed immunochemotherapy in platinum-resistant/refractory ovarian cancer

Cited by 4 publications

References 0 publications

Clinical Activity of Olvimulogene Nanivacirepvec–Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer

Clinical Activity of Olvimulogene Nanivacirepvec–Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer

Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model

Immunotherapy in the Treatment of Platinum-Resistant Ovarian Cancer: Current Perspectives

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