FANG vaccine stalls disease recurrence in ovarian cancer

Issue: May 25, 2015

Treatment with the immunotherapy vaccine FANG was associated with a high rate of T-cell activation and prolonged RFS in patients with stage III/IV ovarian cancer, according to phase 2 study results presented at the Society for Gynecologic Oncology Annual Meeting on Women’s Cancer.

Perspective from Krishnansu S. Tewari, MD

“This is cutting-edge medicine for ovarian cancer,” Jonathan Oh, MD, a gynecologic oncologist at the Texas Oncology–Presbyterian Cancer Center in Dallas, said in a press release. “This immunotherapy may keep the cancer away longer.”

A previous phase 1 trial of the FANG vaccine (Gradalis Inc.) — which is composed of granulocyte-macrophage colony–stimulating factor/bi-shRNAi furin vector-transfected autologous tumor cells — demonstrated safety, T-cell activation and longer survival duration than expected, according to study background. Researchers consider this immunotherapy “bifunctional” because it targets a biochemical pathway in cancer cells and it helps stimulate an immune response in patients to combat the cancer.

Most women with stage III/IV ovarian cancer who receive standard of care — or the combination of debulking surgery and chemotherapy — relapse within 2 years; therefore, Oh and colleagues sought to evaluate the vaccine’s effect on RFS in this population.

The current phase 2 trial consisted of 31 women who achieved a clinical complete response with standard of care treatment. Researchers then randomly assigned patients 2:1 to the FANG vaccine (n = 20) or no maintenance therapy (n = 11).

The researchers harvested cells from the tumor removed during the initial surgery to develop the personalized immunotherapy. Patients assigned the vaccine then received 1 x 10⁷ cells/intradermal injection monthly for up to 12 doses.

Researchers evaluated T-cell activation per interferon-gamma enzyme-linked immunospot assay (ELISPOT). A greater proportion of patients who were chemotherapy-naive achieved interferon-gamma ELISPOT response in the current analysis compared with the previous phase 1 trial (92% vs. 50%).

Overall, patients who did not receive the vaccine had a median cancer recurrence of 14.5 months, whereas patients who received the vaccine have not yet reached a median time to recurrence, and most were well beyond 14.5 months.

Additionally, the vaccine demonstrated an acceptable safety profile, researchers wrote.

“This was a preliminary study with promising results that may give women with advanced ovarian cancer an option for a maintenance regimen,” Oh said in the release.

The study design allowed patients to crossover to the FANG arm if they experienced disease recurrence during the trial period.

“Based on safety, the high rate of T-cell activation in this population in correlation, and the marked delay in time regression, randomization was discontinued and phase 3 testing involving 382 evaluable patients is being pursued,” the researchers wrote. – by Anthony SanFilippo

Reference:

Oh J, et al. Abstract #1. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 28-31, 2015; Chicago.

Disclosure: The study was funded by Gradalis Inc., the manufacturer of the vaccine. Oh reported stock ownership in Gradalis Inc. HemOnc Today was unable to obtain a list of any further relevant financial disclosures from the remaining researchers.

Perspective

Krishnansu S. Tewari, MD

This study provides some insight into a provocative immunotherapy trial in ovarian cancer. Oh and colleagues reported on the efficacy and tolerability of the FANG vaccine, an autologous tumor cell vaccine, studied as a maintenance strategy in women with advanced ovarian cancer who had achieved a complete clinical response. A 2:1 randomization was employed in this phase 2 open-label trial, with vaccines created from tumor directly harvested at the time of primary cytoreductive surgery. Once complete clinical response was achieved, patients received monthly vaccinations (up to 12 injections depending on how much tumor had been available for vaccine preparation). Among the 31 evaluable patients, 20 had been randomly assigned to the investigational arm of the trial. The median time to recurrence for the control group was 14.5 months, whereas the median time to recurrence for the vaccinated group has not yet been reached. Importantly, the majority of the immunotherapy group are beyond 14.5 months in follow-up, and crossover at progression was allowed for the control group. No toxicity was observed.
Epithelial ovarian cancer is the most lethal gynecologic malignancy due to lack of a validated screening tool for the general population, a constellation of nonspecific symptoms early in the disease course, genomic instability and acquired drug resistance. In the United States, there will be approximately 21,000 new cases and nearly 15,000 deaths in 2015. The potential efficacy of the FANG vaccine will require prospective validation with greater numbers of patients. However, this approach is at the heart of personalized medicine, as it derives from an individual patient’s cancer prior to intervening therapy, and it ultimately targets a critical signal transduction pathway in subclinical malignant disease and harnesses innate immunity through immunostimulation.
In summary, Oh and colleagues build upon the immunotherapeutic triad of concurrent autologous antigen provision, immunostimulation and inhibition of autologous whole-cell component endogenous immunosuppression. The findings are noteworthy and advancement to phase 3 trial is justified.

Krishnansu S. Tewari, MD

University of California Irvine Health

Disclosures: Tewari reports no relevant financial disclosures.