FDA Grants Fast Track Designation to VB-111 for Platinum-Resistant Ovarian Cancer


The FDA has granted a fast track designation to VB-111, a targeted anticancer viral gene therapy, for use as a potential therapeutic option in patients with platinum-resistant ovarian cancer.

The FDA has granted a fast track designation to VB-111 (ofranergene obadenovec), a targeted anticancer viral gene therapy, for use as a potential therapeutic option in patients with platinum-resistant ovarian cancer.1

VB-111 is designed to use a dual mechanism to target a wide range of solid tumors, including ovarian cancer. The mechanism pairs the blockade of tumor vasculature with an antitumor immune response. Prior data from a phase 1/2 trial (NCT01711970) indicated that when VB-111 was combined with paclitaxel in this patient population, it was efficacious and safe.2,3

Among the 21 patients enrolled to the trial, approximately half had platinum-refractory disease and half previously received treatment with antiangiogenics. Despite these poor-prognostic characteristics, 58% of evaluable patients experienced CA-125 responses. Moreover, the median overall survival (OS) observed in those who received the agent at the therapeutic dose of 1 x 1013 viral particles plus paclitaxel at 80 mg/m2 (n = 17) was 498 days vs 172.5 days with the sub-therapeutic dose of 3 x 1012 viral particles plus paclitaxel at 40 mg/m2 to 80 mg/m2 (n = 4; P = .03).

The combination is currently under further exploration in the phase 3 OVAL trial (NCT03398655), where it is being compared with paclitaxel alone in patients with recurrent platinum-resistant ovarian cancer.

“We are pleased to receive FDA fast track designation for [VB-111] in platinum-resistant ovarian cancer. The fast track designation can facilitate the process toward potential registration and, importantly, may help expedite the time to market for [VB-111], if approved,” Dror Harats, MD, chief executive officer of VBL Therapeutics, stated in a press release. “The readout of the PFS primary end point in the OVAL trial will be an important milestone for VBL in the second half of [2022]. We believe that, if positive, this will support a biologics license application submission to the FDA.”

OVAL recently completely enrollment of 409 patients, and the trial is being conducted at cancer centers throughout the United States, Europe, Israel, and Japan. To participate, patients needed to be 18 years of age or older with histologically confirmed epithelial ovarian cancer and platinum resistance. Additionally, patients had to have an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1 criteria that required chemotherapy treatment, and acceptable hematologic function.4

Patients were randomized 1:1 to receive VB-111 plus paclitaxel or placebo plus paclitaxel. Intravenous (IV) VB-111 was administered at 1 x 1013 viral particles every 2 months. Both treatment arms received 80 mg/m2 of IV paclitaxel weekly.

The primary end points of the trial were OS and progression-free survival (PFS), and secondary end points included combined CA-125 and RECIST v1.1 response, CA-125 response, objective response rate per RECIST v1.1 criteria, and OS100 for a sensitivity analysis of OS.

In March 2020, OVAL was allowed to continue without modification after an independent data safety monitoring committee (DSMC) determined that the combination hit the prespecified benchmark of an absolute percentage advantage of at least 10% in CA-125 response vs placebo plus paclitaxel.5

Specifically, VB-111 and paclitaxel elicited a CA-125 response rate of 53% in the first 60 evaluable patients across both treatment arms. The response rate in the investigative arm, assuming a balanced randomization, was 58% or higher. Additionally, in those with post-dosing fever, a known marker for VB-111, the reported response rate with the regimen was 69%.

Subsequently, in August 2020, the DMSC evaluated the unblinded OS data collected on the first 100 participants who underwent randomization and had follow up for at least 3 months. Based on these findings, they unanimously recommended that the trial to continue.6 As of November 16, 2020, a high response rate of over 50% in evaluable patients was maintained with approximately 200 patients enrolled, according to the press release.

The following year, in February 2021, the trial received another green light to continue, after a review of unblinded data from 370 randomized patients did not reveal any safety issues.7

A top-line readout of the co-primary end point of PFS is expected in the second half of 2022. The top-line readout for overall survival OS, the other co-primary end point, could occur in the first half of 2023.


  1. VBL Therapeutics receives FDA fast track designation for ofra-vec for the treatment of platinum-resistant ovarian cancer. News release. VBL Therapeutics. April 26, 2022. Accessed April 26, 2022. https://bit.ly/3Lm3mZA
  2. VBL final phase 1/2 study results presented at ASCO demonstrate VB-111 dose dependent Increase in overall survival and 58% CA-125 response rate in platinum-resistant ovarian cancer. News release. VBL Therapeutics. June 3, 2019. Accessed April 26, 2022. https://bit.ly/3axNS2x
  3. Cohen YC, Berlin ST, Birrer MJ, et al. Ofranergene obadenovec (VB-111) in platinum resistant ovarian cancer: association of favorable response rates in a phase I/II study with an immunotherapeutic effect. J Clin Oncol. 2019;37(suppl 15):5542. doi:10.1200/JCO.2019.37.15_suppl.5542
  4. A study of VB-111 with paclitaxel vs paclitaxel for treatment of recurrent platinum-resistant ovarian cancer (OVAL) (OVAL). ClinicalTrials.gov. Updated March 22, 2022. Accessed April 26, 2022. https://clinicaltrials.gov/ct2/show/NCT03398655
  5. VBL Therapeutics announces positive outcome of the interim analysis in the OVAL phase 3 ovarian cancer pivotal study. News release. VBL Therapeutics. March 26, 2020. Accessed April 26, 2022. https://bit.ly/2Cm0Wfr
  6. VBL Therapeutics announces second successful pre-planned interim analysis with a positive data safety monitoring committee review looking at OS – the primary endpoint of the OVAL phase 3 potential registration study of VB-111 in ovarian cancer. News release. VBL Therapeutics. August 12, 2020. Accessed April 26, 2022. https://bit.ly/2XUno6J
  7. VBL Therapeutics announces data safety monitoring committee provides green light to advance the OVAL phase 3 registration enabling study of VB-111 in ovarian cancer. News release. VBL Therapeutics. February 22, 2021. Accessed April 27, 2022. https://bit.ly/3bz6LDE
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