In the phase II VIRO-15 trial reported in JAMA Oncology, Holloway et al found that virotherapy with the modified oncolytic vaccinia virus olvimulogene nanivacirepvec plus platinum-based chemotherapy with or without bevacizumab showed activity in patients with platinum-resistant or platinum-refractory ovarian cancer.
Study Details
In the U.S. multicenter trial, 27 patients (14 with platinum-resistant disease, 13 with platinum-refractory disease) with disease progression following their last prior line of therapy were enrolled between September 2016 to September 2019. The median number of prior lines of therapy was four (range = 2–9).
Patients received olvimulogene nanivacirepvec via temporary intraperitoneal dialysis catheter as two consecutive daily doses (3 × 109 plaque-forming units/d) followed by a platinum doublet with or without bevacizumab. Platinum doublets were selected by investigators from gemcitabine, taxane, or pegylated liposomal doxorubicin coupled with carboplatin or cisplatin. Continued nonplatinum single-agent therapy was encouraged in case of unacceptable platinum toxicity. Bevacizumab was permitted with platinum-doublet or single-agent therapies. The primary outcome measures were objective response, response on CA-125 assay, and progression-free survival.
Efficacy Outcomes
All patients received carboplatin-doublet therapy, except for one who received oxaliplatin-doublet therapy. The nonplatinum agents included gemcitabine (44%), docetaxel (26%), paclitaxel (15%), and pegylated liposomal doxorubicin (15%). Bevacizumab was started with platinum-based therapy in 23 of 27 patients and was given to the remaining four after a delay. All patients completed both olvimulogene nanivacirepvec infusions and chemotherapy. Median follow-up was 47.0 months (95% confidence interval [CI] = 35.9 months to not estimable).
Among 24 evaluable patients, objective response was observed in 54% (95% CI = 33%–74%), with a median duration of response of 7.6 months (95% CI = 3.7–9.6 months); the disease control rate was 88%. The response rate by CA-125 among 26 evaluable patients was 85% (95% CI = 65%–96%).
Among all patients, median progression-free survival was 11.0 months (95% CI = 6.7–13.0 months), with a 6-month rate of 77%. Median progression-free survival was 10.0 months (95% CI = 6.4 months to not estimable) among platinum-resistant patients and 11.4 months (95% CI = 4.3–13.2 months) among platinum-refractory patients.
Among all patients, median overall survival was 15.7 months (95% CI = 12.3–23.8 months). Median overall survival was 18.5 months (95% CI = 11.3–23.8 months) among platinum-resistant patients and 14.7 months (95% CI = 10.8–33.6 months) among platinum-refractory patients.
Adverse Events
The most common treatment-related adverse events of any grade were pyrexia (63.0%, 3.7% grade 3), abdominal pain (51.9%, 7.4% grade 3), and nausea (48.1%). There were no grade 4 treatment-related adverse events, no treatment-related discontinuations of therapy, and no treatment-related deaths. Nonsteroidal anti-inflammatory agents were avoided for up to 3 weeks following olvimulogene nanivacirepvec to minimize inhibition of viral activity; flu-like symptoms, including fever, chills, and myalgia, were usually transient, occurring over hours or overnight.
The investigators concluded, “In this phase II nonrandomized clinical trial, [olvimulogene nanivacirepvec] followed by platinum-based chemotherapy with or without bevacizumab as immunochemotherapy demonstrated promising overall response rates and progression-free survival with a manageable safety profile in patients with platinum-resistant or -refractory ovarian cancer. These hypothesis-generating results warrant further evaluation in a confirmatory phase III trial.”
Robert W. Holloway, MD, and Sarfraz Ahmad, PhD, of AdventHealth Cancer Institute, Orlando, Florida, are the corresponding authors for the JAMA Oncology article.
Disclosure: The study was funded by Genelux Corporation. For full disclosures of the study authors, visit jamanetwork.com.
