The part 3 OVAL scientific trial has been discontinued after the mixture of ofranergene obadenovec and paclitaxel didn’t obtain the research’s major finish factors of enchancment in progression-free and total survival.
The use of ofra-vec (ofranergene obadenovec; VB-111) with paclitaxel as remedy of sufferers with platinum-resistant ovarian most cancers didn’t considerably enhance progression-free survival (PFS) and total survival (OS), lacking the coprimary finish factors of the part 3 OVAL research (VB-111-701/GOG-3018, NCT03398655).1
Topline findings from the randomized, managed, double-arm, double-blind, multi-center OVAL research confirmed that ofra-vec and paclitaxel achieved a median PFS of 5.29 months in contrast with 5.36 months in the management arm (HR, 1.03), in accordance with a press launch by VBL Therapeutics. The median OS noticed in the research was 13.37 months with ofra-vec and paclitaxel vs 13.14 months with paclitaxel alone (HR, 0.97). This consequence didn’t assist continuation of the research.
The outcomes proven a downward trajectory of the trial for the reason that 2020 planned interim analysis of OVAL. At the time, it was introduced that the mixture of ofra-vec and paclitaxel met the pre-specified efficacy criterion of an absolute share benefit of 10% or larger CA-125 response price in sufferers with platinum-resistant ovarian most cancers. In 60 sufferers, the general CA-125 response price was 53%, displaying a 58% larger response vs the management mixture. Also, the response price was 69% amongst sufferers who had post-dosing fever.2
In phrases of security, the addition of ofra-vec to paclitaxel was well-tolerated. Grade ≥ 3 opposed occasions (AEs) have been noticed in 9 sufferers. The commonest AEs noticed in the course of the research have been fatigue (52%), nausea (52%), fever (48%), anemia (38%), diarrhea (33%), and headache (29%). Some circumstances of fever and the anticipated toxicities of angiogenic and taxanes occurred.
Patients in the research acquired 1x10e13 VPs of ofra-vec intravenously each 2 months in mixture with paclitaxel 80 mg/m2 each week in the experimental arm. Patients in the management arm acquired an equal dose of paclitaxel with placebo. In addition to survival, the research sought to evaluate the mixed CA-125 and RECIST 1.1 response, CA-125 response, goal response price by RECIST 1.1, and OS100 for a sensitivity evaluation of OS.
The sufferers enrolled in the research have been aged 18 years or older with histologically confirmed epithelial ovarian most cancers and documented illness that’s platinum resistant. All sufferers had measurable illness per RECIST 1.1, an ECOG efficiency standing of 0 or 1, and sufficient hematological features. The research excluded sufferers who acquired prior radiotherapy to the pelvis or entire stomach or have been handled with greater than 5 anticancer regimens. Patients have been additionally excluded based mostly on sure infections and comorbidities which will have interfered with research remedy.3
“Given the pressing unmet want for these combating platinum-resistant ovarian most cancers, we’re deeply disenchanted that the top-line knowledge point out that ofra-vec didn’t enhance progression-free survival or total survival,” mentioned Dror Harats, MD, chief govt officer of VBL Therapeutics, in a press launch.1 “Based on this end result, we plan to discontinue the OVAL trial and can evaluate the info from our ongoing part 2 trials in metastatic colorectal most cancers and recurrent glioblastoma multiforme to find out subsequent steps with the ofra-vec program.”
Previously, the FDA granted quick observe designation to ofra-ve plus paclitaxel for the treatment of platinum-resistant ovarian cancer. Although the OVAL research won’t proceed, the event of ofra-vec will proceed in different research.
REFERENCES:
1. VBL Therapeutics pronounces top-line knowledge from part 3 OVAL trial of ofra-vec in sufferers with platinum-resistant ovarian most cancers. News launch. VBL Therapeutics. July 19, 2022. Accessed July 20, 2022. https://bit.ly/3OkJjeP
2. VBL ultimate part 1/2 research outcomes introduced at asco display vb-111 dose dependent enhance in total survival and 58% ca-125 response price in platinum-resistant ovarian most cancers [news release]. Tel Aviv, Israel: News Release. VBL Therapeutics. June 3, 2019. Accessed July 20, 2022. https://bit.ly/3ahBZNQ.
3. A research of VB-111 with paclitaxel vs paclitaxel for remedy of recurrent platinum-resistant ovarian most cancers (OVAL) ClinicalTrials.gov. Updated March 22, 2022. Accessed July 20, 2022. https://clinicaltrials.gov/ct2/present/NCT03398655?time period=NCT03398655&draw=2&rank=1
https://www.targetedonc.com/view/ofra-vec-paclitaxel-shows-no-significant-survival-benefit-in-platinum-resistant-ovarian-cancer
