Researchers claim immunotherapy may offer improved outcomes for patients experiencing HRP ovarian cancer.
Historically, homologous recombination proficient (HRP) ovarian cancer is difficult to treat. Those presenting with the disease have few therapeutic opportunities. The therapies that exist present a two-fold problem: They provide minimal benefit to the patient’s well-being and mortality, and they often produce substantial toxin levels. For these reasons, HRP ovarian cancer holds unique challenges for patients, physicians and researchers. Early research on gemogenovatucel-T (Vigil), a maintenance therapy vaccine, suggests a potential solution.
The phase 2b VITAL study established Vigil’s clinical potential. Though involving only a small population, the study produced findings substantial enough to continue pushing forward in the future.
“[Vigil] has the potential to fill an unmet need in ovarian cancer treatment,” says Rodney P. Rocconi, MD, FACOG, professor in the Division of Oncology at the University of Alabama at Birmingham and Associate Director of Clinical Research for Infirmary Health in Mobile, Alabama. “This is an extremely novel agent in the way that it works, and it’s beneficial in our group of patients. It really could change the standard of care for patients with [HRP] disease, where our standard of care really hasn’t changed for 20 years.”
VITAL Methods and Findings
Previous to the recent work undertaken by Dr. Rocconi and others, researchers found Vigil an effective method for extending survival and deterring relapse among patients within the BRCA wild-type, HRP population. VITAL aimed to determine the therapy’s efficacy three years after treatment.
“The entire cancer community is looking at immunotherapy,” Dr. Rocconi says. However, he explains that immunotherapy response has been “very disappointing to date for ovarian cancer, with checkpoint inhibitors having about 10% response rate in ovarian cancer.”
Vigil seems to improve drastically on these results. For the study, 25 patients received Vigil. Another 20 participants received placebo. Patients who received Vigil were administered monthly intradermal vaccines. Depending on various factors, patients received between four and 12 vials of vaccine until completion.
The double-blind, placebo-controlled study concluded that after three years, survival amongst those receiving Vigil greatly outpaced those who did not. Though median overall survival had not yet been achieved at the time of publication, researchers determined it is likely greater than 41 months. This compares favorably to 26.9 months of overall survival for those treated via placebo.
This is significant, as previous efforts to use immunotherapy in the treatment of HRP ovarian cancer were unsuccessful. However, the problem may not be immunotherapy as an entity. It may be the approach.
“It’s not that immunotherapy doesn’t work [on HRP ovarian cancer],” Dr. Rocconi says. “It just hasn’t [had a] specific enough approach.”
When considering the lack of response to traditional therapeutic options, coupled with the toxicity of certain agents, Vigil may secure its position as a maintenance therapy. Its future position as standard of care seems likely, due to the positive results it produced and patient tolerance. Thus far, no patients have reported a grade 3 or 4 adverse event after receiving Vigil.
Root of Success
The excellent performance of Vigil is due, according to Dr. Rocconi, to taking a more specific approach. Upon diagnosis, the vaccine is obtained from ovarian cancer patients and genetically modified to encompass mechanisms with the following purposes:
1. To enhance the presentation of unique tumor-specific antigens. As such, a vaccine created from one patient’s cancer would not be effective for any other patient’s ovarian cancer. Each vaccine is too specific for such overlap.
2. To genetically encode granulocyte-macrophage colony-stimulating factor, which aids in recruiting more immune cells to the tumor microenvironment, resulting in a more globalized, robust immune response.
3. To suppress TGFβ1 and TGFβ2, which are strongly articulated in ovarian cancer and lead to adverse prognosis. Suppression takes place via bifunctional, short-hairpin RNA targeted to furin.
Thus far, it seems Vigil performs these tasks well. However, as a 20-year member of the Society of Gynecologic Oncology who has served on numerous committees and task forces, Dr. Rocconi is only cautiously optimistic about Vigil’s potential applications for HRP ovarian cancer care.
“Vigil showed significant response, but in a small group of patients,” he says. “What we hope and believe is happening is that this technology is allowing patients to live longer, healthier lives. We hope this translates to more cures, but the data is too immature [at this time] to say such.”
Further Investigation Required
As the autologously derived vaccine aimed at the patient’s specific neo-antigens is the crux of Vigil, it is unlikely that researchers will develop an off-the-shelf, allogenic version of Vigil. Such an option would likely not provide a robust response within HRP ovarian cancer patents. That said, to achieve a more mature data set with the potential to change therapeutic guidelines, a number of questions must be answered.
To date, it is unknown whether a vaccine regimen of four or 12 doses is most efficient. Or perhaps another prescription and/or dosage will provide even more benefit. To begin answering these and other questions, a larger number of HRP ovarian cancer patients must be studied via a phase 3 controlled trial.
Currently, Dr. Rocconi and others are awaiting funding to begin further investigation. Once the study begins, researchers hope to involve approximately 800 patients at 100 or more sites across the United States. Providers are encouraged to refer patients or consider opening the trial at their own sites.
Visit clinicaltrials.gov for the latest status updates on the phase 3 study.