Treatment with an investigational targeted anti-cancer gene-therapy agent, VB-111, in addition to paclitaxel met the pre-specified efficacy criterion of an absolute percentage advantage of 10% or higher CA-125 response rate in patients with platinum-resistant ovarian cancer, according to results from the planned interim analysis of the phase III OVAL trial.<br />
Treatment with an investigational targeted anticancer gene-therapy agent, VB-111, in addition to paclitaxel met the pre-specified efficacy criterion of an absolute percentage advantage of 10% or higher CA-125 response rate in patients with platinum-resistant ovarian cancer, according to results from the planned interim analysis of the phase III OVAL trial (NCT03398655) announced in a press release by VBL Therapeutics.1
“The encouraging interim readout in this randomized controlled study, together with the promising data seen in the earlier VB-111 phase II are signals for the potential of VB-111 in platinum-resistant ovarian cancer, an indication with a major unmet need," said the chairman of the OVAL study Steering Committee, Bradley J. Monk, MD, FACS, FACOG, in the press release. Monk is a co-director of GOG Partners, Arizona Oncology (US Oncology Network); professor of Gynecologic Oncology at the University of Arizona, Creighton University; and medical director of the US Oncology Research Gynecology Program in Phoenix, Arizona,
Overall, 60 patients were evaluable for response, and the overall CA-125 response rate was 53%. Under the assumption that randomization was balanced between the VB-111 treatment arm and the paclitaxel monotherapy arm, the response rate is 58% or higher with the combination. The response rate was 69% in patients who had a post-dosing fever, a marker for VB-111 treatment.
In a previous phase I/II study, VB-111 showed similar efficacy with a statistically significant overall survival (OS) observed with a therapeutic dose of the drug versus a low dose of the drug (498 vs 172.5 days, P= .03). Additionally, 58% of the patients had a CA-125 response, which was found to be predictive of OS in patients treated with a therapeutic dose of VB-111. A factor observed and associated with favorable OS was fever response to VB-111, which occurred in 29% of patients.2
Notably, the OS observed in the phase I/II study was double the OS observed with the agent historically.3
In terms of safety, VB-111 was well tolerated in the study population, except for fever and the anticipated toxicities of angiogenic and taxanes. Overall, 9 patients reported adverse events (AEs) grade ≥3. The most common AEs observed were fatigue (52%), nausea (52%), fever (48%), anemia (38%), diarrhea (33%), and headache (29%).
Investigators concluded from the study that the efficacy signal was encouraging and would be further explored in the OVAL study.
The randomized, controlled, double-arm, double-blind, multi-center OVAL study aims to enroll 400 patients with recurrent platinum-resistant ovarian cancer. The primary end point was OS and the secondary end points were progression-free survival, combined CA-125 and RECIST 1.1 response, CA-125 response alone, and objective response rate.1
Patients are eligible for the OVAL study granted they have histologically confirmed epithelial ovarian cancer and documented disease, platinum-resistant disease, and measurable disease per RECIST 1.1 criteria. These patients are required to have an ECOG performance status of 0 to 1 and adequate hematologic functions.
The study excluded patients with non-epithelial tumors, ovarian tumors with low malignant potential, and those with a history of another clinically active malignancy within 5 years of enrollment in the study. Patients were also ineligible if they had more than 5 prior anticancer regimens, brain metastases, active infection, or diseases that can potentially interfere with treatment in the study.
“We are very pleased by the outcome of this interim analysis, which demonstrates the potential benefit of VB-111 over standard-of-care in a randomized-controlled study,” said Dror Harats, MD, chief executive officer of VBL Therapeutics, in a statement. “The OVAL phase III interim data are at least as good as the CA-125 response results observed in our VB-111 phase II study, which enrolled a similar patient population. This encouraging interim result adds to the promising data seen with VB-111 across our phase II studies in multiple indications.”