In the phase IIb VITAL trial reported in The Lancet Oncology, Rocconi et al found that front-line maintenance with the autologous tumor cell vaccine gemogenovatucel-T did not improve recurrence-free survival vs placebo in patients with stage III/IV ovarian cancer in clinical complete response after undergoing a combination of surgery and chemotherapy. However, a benefit was observed in the subgroup of patients with BRCA wild-type disease. Gemogenovatucel-T is an autologous tumor cell vaccine manufactured from harvested tumor tissue that reduces expression of furin and downstream TGF-β1 and TGF-β2.

Study Details

In the U.S. multicenter double-blind study, 91 patients (per-protocol population) were randomly assigned between February 2015 and March 2017 to receive gemogenovatucel-T (n = 47) or placebo (n = 44). Patients had stage III/IV high-grade serous, endometrioid, or clear cell ovarian cancer, and were in clinical complete response after a combination of surgery and five to eight cycles of neoadjuvant or adjuvant chemotherapy involving carboplatin and paclitaxel. Treatment consisted of gemogenovatucel-T at 1×10⁷ cells per injection or placebo given intradermally once per month for a minimum of 4 and up to 12 doses. The primary endpoint was recurrence-free survival from time of random assignment in the per-protocol population. Secondary endpoints included recurrence-free survival of patients with BRCA wild-type disease from time of surgery/tumor tissue procurement and from time of random assignment.

Recurrence-Free Survival

Median follow-up was 40.0 months from the first dose of gemogenovatucel-T and 39.8 months from the first dose of placebo. Patients in both groups received a median of six injections.

Median recurrence-free survival from time of random assignment was 11.5 months (95% confidence interval [CI] = 7.5 months–not reached) in the gemogenovatucel-T group vs 8.4 months (95% CI = 7.9–15.5 months) in the placebo group (hazard ratio [HR] = 0.69, 90% CI = 0.44–1.07, P = .078).

Among the 40 (85%) patients in the vaccine group vs the 27 (61%) patients in the placebo group with BRCA wild-type disease, recurrence-free survival was longer in the gemogenovatucel-T group from time of tissue procurement (HR = 0.64, 90% CI = 0.42–1.00, P = .048), with 1- and 2-year rates of 81% vs 63% and 42% vs 24%, and from time of random assignment (HR = 0.51, 90% CI = 0.30­–0.88, P = .020), with 1- and 2-year rates of 51% vs 28% and 33% vs 14%.

Adverse Events

The most common treatment-related adverse events of any grade in the gemogenovatucel-T group were injection site reaction (34% vs 16% in placebo group) and arthralgia (11% vs 14%). No grade 3 or 4 treatment-related adverse events were observed in the gemogenovatucel-T group. Two patients in the placebo group had a total of five grade 3 treatment-related events, consisting of arthralgia, bone pain, generalized muscle weakness, syncope, and dyspnea. Serious adverse events occurred in three patients (6%) vs four patients (9%). No treatment-related deaths were reported in either group.

The investigators concluded, “Front-line use of gemogenovatucel-T immunotherapy as maintenance was well tolerated, but the primary endpoint [of the trial] was not met. Further investigation of gemogenovatucel-T in patients stratified by BRCA mutation status is warranted.”

John Nemunaitis, MD, of the Department of Medical Affairs, Gradalis, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Gradalis. For full disclosures of the study authors, visit thelancet.com.