Dr Leary on a Neo-Epitope-Based Vaccine With or Without Pembrolizumab in Platinum-Sensitive Recurrent Ovarian Cancer

“We improved PFS significantly with this combination as maintenance compared with best supportive care, diminishing the risk of progression by almost 50% with a highly significant P value.”

Alexandra Leary, MD, PhD, deputy head of the Department of Medical Oncology and chair of the GINECO group at Gustave Roussy, discussed progression-free survival (PFS) and safety data from the phase 2 TEDOVA/GINECO-OV244b/ENGOT-ov58 trial (NCT04713514) evaluating the neo-epitope vaccine Tedopi (OSE2101) alone or with pembrolizumab (Keytruda) as maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer previously treated with a PARP inhibitor and bevacizumab (Avastin).

The academic trial enrolled 185 patients with non-mucinous, platinum-sensitive relapsed ovarian cancer who had responded to or had disease control with platinum-doublet chemotherapy, were HLA-A2 positive, and had prior PARP inhibitor and bevacizumab exposure or a contraindication, Leary said. Patients were randomly assigned 1:1:2 to best supportive care (n = 45), Tedopi alone (n = 45), or Tedopi plus pembrolizumab (n = 90) for up to 2 years, with PFS as the primary end point. PFS was met, with the combination reducing the risk of progression or death by 47% vs best supportive care (HR, 0.53; 95% CI, 0.36-0.78; P < .001), with median PFS values of 4.11 months (95% CI, 2.99-5.45) vs 2.76 months (95% CI, 2.3-2.86), respectively.

Although not powered for pairwise testing, the trial showed a nonsignificant PFS benefit with Tedopi alone vs best supportive care (HR, 0.70; 95% CI, 0.46-1.08; P = .099) and an incremental benefit for the combination vs Tedopi alone (HR, 0.72; 95% CI, 0.5-1.04; P = .074), Leary said. Baseline characteristics were balanced: over 50% of patients were homologous recombination deficient, approximately half had a complete or partial response to platinum-based chemotherapy and half had stable disease, and 85% had received both a PARP inhibitor and bevacizumab, with the rest having a contraindication to one.

Leary reported a numerical increase in immune-related toxicity, mostly grade 1/2, with the addition of pembrolizumab, most often injection-site reactions. Cytokine release syndrome (CRS), rare with a vaccine alone, occurred in 9% of patients on Tedopi monotherapy vs 28% on the combination, predominantly grade 1/2, which Leary said suggested immune synergy between the agents. Adding prophylaxis with paracetamol and NSAIDs midway through the trial reduced grade 1/2 CRS, she noted.

Leary called TEDOVA the first proof-of-concept for a vaccine strategy in ovarian cancer and the first positive randomized trial in the platinum-sensitive setting in some time. She noted that patients on best supportive care alone historically have a postplatinum PFS of 2.3 months, underscoring the unmet need in this population. Translational analyses are ongoing, Leary said.