Treatment with the immunotherapy Vigil delayed time to progression in all patients with stage III/IV ovarian cancer who were treated with the autologous tumor cell vaccine compared with those who were not in an open-label phase II trial.
Jonathan Oh, MD
Treatment with the immunotherapy Vigil, formally known as FANG, delayed time to progression in all patients with stage III/IV ovarian cancer who were treated with the autologous tumor cell vaccine compared with those who were not, according to an open-label phase II trial.
In the 31-patient trial, which was presented at the 2015 SGO Annual Meeting, patients were randomized to receive the vaccine or no treatment following surgery. Of the 20 patients who received the vaccine, a median time to progression had not yet been reached compared with a median of 14.5 months in those who were not treated.
Additionally, the Vigil vaccine, composed of granulocyte macrophage colony-stimulating factor [GM-CSF] bi-shRNAi furin vector-transfected autologous tumor cells, demonstrated an acceptable safety profile, and participants showed a high rate of immune response via T-cell activation.
Lead author Jonathan Oh, MD, of Texas Oncology in Dallas, called the study findings encouraging. “Results in phase II ovarian cancer suggest Vigil-mediated prolongation of time to recurrence,” he said during a scientific plenary session.
A preceding trial discovered longer-than-expected survival duration that correlated with ELISPOT reactivity. This earlier trial examined a variety of advanced tumors, ranging from adenoid cystic carcinoma to synovial sarcoma. Ovarian cancers represented a small percentage of the study total.
“We believe further randomized assessment is justified based on a 93% ELISPOT [Enzyme-Linked ImmunoSPOT assay] conversion in phase II to minimal residual disease in ovarian cancer. That’s compared to a phase I result of 54% conversion in patients with bulky disease.”
Oh et al narrowed the phase II study’s focus to ovarian cancer for several reasons. “Approximately 75% of stage III/IV patients with ovarian cancer who achieve clinical complete response (cCR) relapse within 2 years, and there is no standard of care for maintenance therapy,” he noted. “We thought there was potential to determine regression-free survival (RFS) difference by running a 2:1 randomized phase II trial.”
Study participants were patients with stage III/IV ovarian cancer who achieved cCR following surgical debulking and chemotherapy. Tumor tissue was harvested during surgical debulking to use in vaccine construction. Once patients achieved cCR and were confirmed to be ELISPOT-negative, 20 patients were randomized to receive the Vigil treatment, and 11 patients were randomized to the non-Vigil group.
Patients in the active treatment group received 1.0 x 107 cells/intradermal injection once monthly for up to 12 doses. Patients in the control group received no maintenance therapy. The trial design allowed for patients to be transferred to the active treatment group if they experienced disease progression during the trial.
Adverse events (AEs) were minimal. During phase I, phase II, and phase II crossover combined, 50 patients with ovarian cancer received a total of 141 Vigil injections. No grade 3 or 4 AEs were recorded in the phase II study. Only one grade 2 AE was reported (erythema). The most common grade 1 AEs were indurations (28), injection-site reactions (14), and erythema (23).
The phase II trial’s key endpoints were patient safety, immune response, and RFS. Noting that the historical average of RFS is 13 to 18 months, the team discontinued this trial when the active treatment group’s median RFS reached 19.3 months compared with 12.4 months in the control group.
With the 3-year disease-recurrence rate of 60% in the active treatment group compared with 91% in the control group, researchers will pursue a phase III trial involving 382 evaluable patients.
“It’s especially important to note that approximately 93% of patients demonstrated T-cell activation against their tumor antigen as early as 1 month after vaccination,” Oh said. “This is an area of great potential.”
In February 2015, a phase III study was initiated to explore Vigil as a treatment for women with stages III/IV high-grade ovarian cancer following cytoreduction and 5 to 6 cycles of standard of care chemotherapy. The company developing the vaccine, Gradalis, plans to submit findings from this study to regulatory authorities, if they are positive.
Oh J, Barve M, Grosen EA, et al. Randomized phase II trial of maintenance autologous tumor cell vaccine (FANGTM) following clinical complete response (cCR) in stage III/IV ovarian cancer: preliminary results. Presented at: Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer 2015; March 28-31, 2015; Chicago, IL. Abstract No 1.