Results of the phase 2b VITAL trial suggest that immunotherapy with the autologous tumor cell vaccine gemogenovatucel-T as frontline maintenance in stage III/IV ovarian cancer is well-tolerated and shows clinical benefit in both BRCA-wild type and homologous recombination–proficient subgroups.
The double-blind, placebo-controlled, phase 2b VITAL (NCT02346747) trial demonstrated recurrence-free survival (RFS) benefit with maintenance therapy of the autologous tumor-cell vaccine, gemogenovatucel-T (GEM), following frontline platinum-based chemotherapy in patients with advanced high-grade ovarian cancer. Post-hoc homologous recombination deficiency (HRD) subgroup analysis and identification of an additional molecular subgroup sensitive to GEM were reported at the 2021 American Society of Clinical Oncology Annual Meeting.
This study enrolled patients with newly diagnosed stage III/IV epithelial ovarian cancer, who achieved a clinical complete response to frontline surgery and platinum-based chemotherapy. Eligible patients received 1 × 107 cells/mL of GEM or placebo intradermally once a month, for up to 12 doses or until disease progression. The primary end point was RFS, assessed by blinded independent central review. HRD status was determined according to the Myriad Genetics myChoice CDx assay (HRD score <42 for proficient). A protein–protein interaction network was constructed using the STRING database and tumor annotated DNA polymorphism data. The per-protocol population included 91 patients.
Of the 62 evaluable patients assessed for HRD status, 45 patients were homologous recombination proficient, and 17 were homologous recombination deficient; 25 of 45 homologous recombination proficient patients received GEM, and 20 received placebo. The 2 groups were mostly well-balanced, except for a higher proportion of patients with Eastern Cooperative Oncology Group performance status of 0 in the placebo group.
GEM, as first-line maintenance therapy in patients with ovarian cancer, was well-tolerated. The incidence of grades 1 to 3 adverse events was similar in the 2 groups; 63.2% in the GEM group and 59.6% in the placebo group. Among all patients, those in the GEM group showed significant benefit in median RFS (11.5 vs 8.4 months; hazard ratio [HR], 0.688; P = .078), which did not translate into overall survival (OS) benefit (not reached vs 16.0 months; HR, 0.630; P = .110). In the homologous recombination proficient subgroup, from the time of randomization, median RFS was significantly improved with GEM compared with placebo (10.6 vs 5.7 months; HR, 0.386; P = .007). The OS in the GEM/homologous recombination proficient group was significantly higher than that in the placebo/homologous recombination proficient group (HR, 0.417; P = .02); 2-year OS was 92% in the GEM group, compared with 55% in the placebo group (P = .002); and 3-year OS was 70% and 40% (P = .019), respectively. STRING analysis of the homologous recombination proficient/p53-mutated subgroup demonstrated improvement in RFS and OS.
These results suggest that immunotherapy with the autologous tumor cell vaccine GEM as frontline maintenance in stage III/IV ovarian cancer is well-tolerated and shows clinical benefit in both BRCA wild-type and homologous recombination proficient subgroups.
Source: Rocconi RP, Ghamande SA, Barve MA, et al. Maintenance vigil immunotherapy in newly diagnosed advanced ovarian cancer: efficacy assessment of homologous recombination proficient (HRP) patients in the phase IIb VITAL trial. J Clin Oncol. 2021;39(suppl_15). Abstract 5502.