Olvimulogene nanivacirepvec (Olvi-Vec) is an oncolytic virus that is modified to improve tumor selectivity and antitumor activity. The agent activates oncolysis resulting in the immunogenic death of cancer cells and generates immune system response for ongoing tumor-directed immunotherapy. The VIRO-15 trial is a multicenter, open-label, nonrandomized phase 2 study of intraperitoneal Olvi-Vec followed by intravenous carboplatin-doublet ± bevacizumab in 27 pretreated platinum-resistant/refractory ovarian cancer patients. Patients received 2 consecutive days of infused intraperitoneal Olvi-Vec, followed by carboplatin-doublet ± bevacizumab (mean cycles were 6 ± 3), and then maintenance single agent ± bevacizumab.
The patients’ median age was 62 years. Histology grades represented in this study were high, intermediate, and mixed in 92%, 4%, and 4% of patients, respectively. All patients had Eastern Cooperative Oncology Group performance score of 0 or 1. The median number of total previous lines of therapy was 4 (range, 2-9) with a median number of prior platinum-containing lines of 2 (range, 1-5). At baseline, 48% (13) of patients were categorized as platinum-resistant and 52% (14) were platinum-refractory. At the time of enrollment, 81% (22) of patients had undergone prior bevacizumab treatment, and 74% (20) had prior poly (ADP-ribose) polymerase (PARP) inhibitor therapy. The baseline biomarker status of the patients was 4% (1) with positive tumor PD-L1 expression, 92% (25) with negative PD-L1 expression, and in 4% (1) of patients the PD-L1 was unknown. BRCA1/2 mutations were present in 30% (8) of the patient population.
Safety profile revealed the incidence of the following grade 1 and 2 treatment-emergent adverse events (TEAEs): pyrexia, 59% (16); nausea, 48% (13); abdominal distension, 44% (12); abdominal pain, 44% (12); chills, 37% (10); fatigue, 33% (9); and vomiting, 26% (7). Grade 3 adverse events occurring in at least 2 patients included abdominal pain in 7% (2) and hypophosphatemia in 7% (2). No grade 4 TEAEs were reported.
The primary end points of the VIRO-15 study were overall response rate (ORR) measured by RECIST 1.1 and by CA-125, as well as progression-free survival (PFS). The RECIST ORR in all patients was 54% (13/24); in platinum-resistant patients it was 60% (6/10); and in patients with platinum-refractory disease it was 50% (7/14). The CA-125 ORR was 85% (22/26) in all patients, 85% (11/13) in platinum-resistant patients, and 85% (11/13) in patients with platinum-refractory disease. Median PFS was 11 months in all patients, 11 months in platinum-resistant patients, and 10.8 months in platinum-refractory patients. The duration of response in all patients was 7.6 months, 7.6 months in platinum-resistant patients, and 8 months in platinum-refractory patients. Median overall survival was 15.7 months, 17.4 months, 15.2 months in all patients, platinum-resistant, and platinum-refractory, respectively. The disease control rate was 86% in all patients.
Investigational analysis by multiplex immunohistochemistry showed significant permeation of tumor deposits by CD4+ and CD8+ T-cells, while immune response assessment in virotherapy tumor biopsies and blood samples revealed activation of intratumoral CD8+ tumor-infiltrating lymphocytes and the presence of tumor-specific T-cells in the periphery, respectively. The analysis data also reflect that Olvi-Vec stimulates intratumoral STAT1 gene expression via the interferon pathways, which positively impacts the tumor microenvironment.
The study conclusions reveal that patients treated with Olvi-Vec who have pretreated platinum-resistant/refractory ovarian cancer and have been heavily pretreated experienced improved ORR and PFS compared with prior therapies.
Abstract 837P. ESMO 2020. September 19-21, 2020. Phase II trial of oncolytic vaccinia virus primed immunochemotherapy in platinum-resistant/refractory ovarian cancer (PRROC) (NCT02759588).