Novel Gene Therapy Demonstrates Potential for Ovarian Cancer Treatment

September 4, 2020
Kristen Coppock, MA, Managing Editor

Directions in Pharmacy, August 2020, Volume 2, Issue 4

A first-in-class targeted therapy, VB-111 is administered by intravenous infusion once every 6 to 8 weeks.

An investigational anticancer gene therapy has shown potential for treating platinum-resistant ovarian cancer. A recent study found ofranergene obadenovec (VB-111; VBL Therapeutics) to be well tolerated in more than 300 patients with this cancer.1

A first-in-class targeted therapy, VB-111 is administered by intravenous infusion once every 6 to 8 weeks. The drug has a dual mechanism of action: apoptosis of angiogenic endothelium and vascular disruption that leads to tumor starvation and induction of an antitumor-directed immune response.1

The OVAL study (NCT033986552) is a phase 3 randomized, double-blind clinical trial of VB-111 in up to 400 patients across 95 sites.1 Its goal is to compare VB-111 and paclitaxel with placebo and paclitaxel in adult patients with recurrent platinum-resistant ovarian cancer.2 The primary end point is overall survival (OS), with secondary end points of progression-free survival, and objective response rate by cancer antigen 125 (CA-125) and RECIST response.1

This study compared the CA-125 objective response rate (ORR) according to Gynecologic Cancer InterGroup criteria in the treatment and control arms among the first 60 evaluable patients. According to VBL Therapeutics, the CA-125 ORR in those patients was 53%, and, assuming a balanced randomization, the response rate in the treatment arm (VB-111 in addition to weekly paclitaxel) was 58% or higher. In patients with postdosing fever, a marker for VB-111 treatment, the response rate was 69%.1,3

Tami Rachmilewitz, MD, vice president of clinical development for VBL Therapeutics in Israel, said the interim data from OVAL are very encouraging. They demonstrate the potential benefit of VB-111 over standard of care in a randomized, controlled setting, she added in a prepared statement.3

The CA-125 response rate observed in the phase 3 interim analysis is at least as good as the response rate in the prior phase 2 study that enrolled a similar patient population and showed OS benefit, according to investigators. In the previously reported phase 2 study of VB-111 in platinum-resistant ovarian cancer, 58% of the patients treated with VB-111 and paclitaxel demonstrated a CA-125 response. Those patients with a CA-125 response demonstrated a median OS of 808 days compared with survival of 351 days for those patients without a CA-125 response.3

The most recent study was conducted in collaboration with the GOG Foundation, an independent, nonprofit organization that aims to promote excellence in the quality and integrity of clinical and basic scientific research.3

The results of the OVAL analysis were presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program.1,3

Further interim analysis is expected to be conducted in the third quarter of 2020.1 According to Rachmilewitz, more than 25% of the patients are already enrolled in the OVAL study, which is expanding to Europe and Japan this year.3

REFERENCES

  • Arend RC, Monk BJ, Burger RA et al. Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018): results of pre-planned CA-125 response interim analysis. Poster presented at: 2020 American Society of Clinical Oncology Virtual Science Program; May 29-31, 2020. Accessed July 22, 2020. https://meetinglibrary.asco.org/record/191693/poster
  • A study of VB-111 with paclitaxel vs paclitaxel for treatment of recurrent platinum-resistant ovarian cancer (OVAL). ClinicalTrials.gov. Updated June 30, 2020. Accessed July 22, 2020. https://clinicaltrials.gov/ct2/show/NCT03398655?term=OVAL&draw=2&rank=2
  • VBL presents positive interim data from the OVAL phase 3 pivotal study in ovarian cancer at the ASCO20 annual meeting, showing 58% or higher objective response rate. News release. VBL Therapeutics. June 1, 2020. Accessed July 22, 2020. http://ir.vblrx.com/news-releases/news-release-details/vbl-presents-positive-interim-data-oval-phase-3-pivotal-study