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.
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.
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%.
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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.