AUTOLOGOUS VACCINE FOR OVARIAN CANCER

An experimental vaccine tailor-made to a patient's individual tumor is generating excitement and hope that science has finally found a way to improve survival odds in advanced ovarian cancer, say researchers presenting results from a small phase 2 study.

The study was presented during the Society of Gynecologic Oncology's (SGO's) annual meeting on women's cancer in Chicago.

"There is a lot of excitement and hope around the vaccine," principal investigator Jonathan Oh, MD, Texas Oncology, PA, Dallas, told Medscape Medical News.

"But it would be really premature to say the vaccine is effective in advanced ovarian cancer with a phase 2 study like this, so that's the entire purpose of the phase 3 study — to prove that it is," he said. A phase 3 study involving 328 patients is planned.

"For 30-plus years, our standard approaches involving surgery and chemotherapy and even new chemotherapy drugs have not improved survival in this disease," SGO spokesman Krishnansu Tewari, MD, University of California, Irvine, Medical Center, in Orange, told Medscape Medical News.

"And while it's very easy to get excited when you see that among patients who have been vaccinated, the cancer still hasn't come back, the bottom line is, we really need a phase 3 trial before we can get really excited," Dr Tewari said.

New Option for Maintenance Regimen

The phase 2 study included 31 women with stage III or IV ovarian cancer.

All patients had achieved a cytologic complete response following surgical debulking and chemotherapy.

Twenty patients received immunotherapy with their personalized vaccine, and 11 did not.

Injections were given once a month for up to 12 doses.

Control patients were followed with standard of care.

Among women who did not receive the vaccine, the cancer recurred in a median of 14.5 months.

Those who did receive the vaccine had not yet reached the median time to recurrence at the time Dr Oh presented the study, and the majority of vaccine recipients are now well beyond 14.5 months of follow-up.

The vaccine was very well tolerated, as Dr Oh pointed out.

"You have to keep in mind that the numbers of patients in this study are so small that this difference did not reach statistical significance," he cautioned.

"But it's a promising trend, and it suggests that we may be able to give women with advanced ovarian cancer an option for a maintenance regimen."

In ovarian cancer, after an initially good response to up-front treatment, the relapse rate is well over 80%, and patients who experience relapse are generally considered to be incurable, he explained.

FANG Vaccine

The vaccine is referred to as the FANG vaccine and is composed of granulocyte macrophage colony-stimulating factor plus bi-shRNAi furin vector transfected autologous tumor cells.

A previous phase 1 safety study demonstrated that the FANG vaccine was safe.

It also showed that the vaccine did activate T-cells, as confirmed by gamma interferon–enzyme-linked immunospot assay (ELISPOT) positivity.

Importantly, however, the phase 1 study was made up of a "grab bag" of patients with different tumors, including colon cancer, thyroid cancer, and ovarian cancer, and only about half of the ovarian cancer patients in the phase 1 trial had undergone surgery to achieve minimal residual disease.

When tested for evidence of T-cell activation with ELISPOT, only about 50% of this subgroup of phase 1 patients demonstrated evidence of immune activation, compared with 92% of patients in the current phase 2 trial.

As Dr Oh emphasized, all patients in the phase 2 study had minimal residual disease following surgical debulking.

"This suggests that surgery is important to help promote immune activation from the vaccine," Dr Oh said.

To prepare the vaccine, a tumor sample is initially harvested during surgical debulking and is later modified in the laboratory so that it is primed to elicit a highly robust immune response following vaccination.

The FANG vaccine is also "bifunctional," because it targets not only the patient's tumor directly but also blocks certain mediators of immune stimulation.

This additional function enhances the immune system's response to the same tumor antigens.

When the cancer recurs, as it almost invariably does, the revved-up immune system recognizes the custom-tailored tumor antigens and is able to eradicate recurring tumor cells.

Asked whether it is feasible to create a personalized vaccine for every patient with advanced ovarian cancer, Dr Tewari noted that the vaccine can be very easily prepared.

"If the phase 2 study shows that the vaccine leads to a significant improvement in survival, there's a very good chance that the Food and Drug Administration will approve it, and then the vaccine would have to be made available," he speculated.

"Results so far are very promising," Dr Tewari said.

"And now we need to validate this in a much larger phase 2 randomized clinical trial."

The study was funded by Gradalis. Dr Oh is a shareholder in Gradalis. Dr Tewari was not involved in the trial and has declared no relevant financial relationships.

SGO's Annual Meeting on Women's Cancer. Abstract 1. Presented March 28, 2015.