The combination of the neo-epitope vaccine OSE2101 and pembrolizumab (Keytruda) significantly improved progression-free survival (PFS)vs best supportive care (BSC) as maintenance therapy in patients with platinum-sensitive ovarian cancer (PSOC) previously treated with a PARP inhibitor and bevacizumab (Avastin), marking the first positive randomized trial in this setting in several years, according to Alexandra Leary, MD, PhD.1
PSOC previously exposed to a PARP inhibitor and bevacizumabcurrently has no approved maintenance option, and no randomized trial of an immune checkpoint inhibitor, PARP inhibitor, or bevacizumab combination has improved outcomes in this setting over the past 5 years.2 Patients who progress after PARP inhibition also respond poorly to platinum rechallenge, with a correspondingly poor prognosis.3
Data from the phase 2 GINECO-ov244b/ENGOT-ov58/TEDOVA trial (NCT04713514), presented at the 2026 ASCO Annual Meeting, showed that when the neo-epitope vaccine OSE2101 (n = 91)was combined with pembrolizumab (Keytruda), it significantly improved progression-free survival (PFS) over best supportive care (BSC; n = 48) as maintenance in evaluable patients with PSOC and prior exposure to a PARP inhibitor and bevacizumab (n = 185).1 The median PFS in the respective arms was 4.11 months (95% CI, 2.99-5.45) vs 2.76 months (95% CI, 2.3-2.86; HR, 0.53; 95% CI, 0.36-0.78; P < .001). The median PFS with OSE2101 alone (n = 46) was 2.89 months (95% CI, 2.73-4.73; vs BSC: HR, 0.70; 95% CI, 0.46-1.08; P = .099).
“This is the first proof of concept for a vaccine strategy in ovarian cancer, and the first randomized study that's positive in the platinum-sensitive setting in a long time,” Alexandra Leary, MD, PhD, said.“We showed that the combination of the vaccine with pembrolizumab significantly improved PFS, and we confirmed that this patient population represents a real area of unmet medical need, since patients who received only [BSC] had a PFS of 2.3 months post-platinum. Translational work is ongoing”
In an exclusive interview with OncLive®, Leary, who is thedeputy head of the department of medical oncologyand an oncologist specializing in gynecologic cancers at Gustave Roussy in Villejuif, France, discussed the TEDOVA trial's design, the safety profile of the approaches evaluated, and implications for immune-based maintenance strategies in ovarian cancer.
OncLive: What was the rationale for developing OSE2101 as maintenance in platinum-sensitive ovarian cancer?
Breaking the Losing Streak: TEDOVA’s 3 Key Takeaways
- OSE2101 plus pembrolizumab significantly improved PFS vs best supportive care (HR, 0.53; P < .001) as maintenance in platinum-sensitive ovarian cancer.
- Grade 1/2 CRS was more common with the combination than the vaccine alone (28% vs 9%), but incidence declined after paracetamol/NSAID prophylaxis was added.
- TEDOVA is the first positive randomized trial in the platinum-sensitive setting in years, following a string of negative phase 3 checkpoint inhibitor trials.
Leary: The rationale [to conduct this research] was that [PSOC] is an area of unmet medical need. It used to be that we could give platinum again and again and it would work, but now that we've moved maintenance strategies such as PARP inhibitors and bevacizumab into earlier lines—sometimes all in the first line—patients who relapse after platinum-sensitive disease are offered a platinum doublet, but we don't have any approved maintenance strategies for them. We also know that patients who relapse post-PARP have a poor prognosis; even if you reintroduce platinum, they might respond, but the response is very short in duration. Finally, in the past 5 or 6 years, we haven't had a single positive randomized trial in the platinum-sensitive setting, despite large phase 3 trials investigating immune checkpoint inhibitors alone, with a PARP inhibitor, with bevacizumab, or with both; they've all been negative.
Anti–PD-1s alone haven't provided the answer, so we were interested in a different strategy, which is where we started investigating a vaccine called OSE2101. It's a cocktail of tumor-associated antigens modified to increase their binding affinity to both the T-cell receptor and HLA-A2, and the aim of this vaccine is to turn immune-cold tumors, such as ovarian cancer, into immune-hot [tumors]. Patients need to be HLA-A2 positive for this vaccine. We were also encouraged by positive results in lung cancer, where this vaccine improved overall survival in a phase 3 randomized trial in non–small cell lung cancer resistant to immune checkpoint inhibitors. With all of that in mind, we wanted to investigate the benefit of combining this vaccine with an immune checkpoint inhibitor, pembrolizumab, as maintenance in patients with this unmet medical need: platinum-sensitive relapsed ovarian cancer after PARP inhibitors and bevacizumab.
What was the trial design of TEDOVA, and what were the key findings?
We recruited patients with any histology, nonmucinous, who were in platinum-sensitive relapse, had either a response or disease control with the platinum doublet, were HLA-A2 positive, and had prior exposure to both a PARP inhibitor and bevacizumab, or a contraindication to one. They were randomized 1:1:2 to standard of care, which is [BSC] as maintenance; the vaccine alone; or the combination of the vaccine with pembrolizumab for up to 2 years.
The primary endpoint was [PFS], and we powered the study with 185 patients to detect, with 90% power, an improvement in PFS for the combination vs[BSC] at a hazard ratio of 0.57. The primary endpoint was met: we improved PFS significantly with the combination as maintenance compared with [BSC], [reducing] the risk of progression by almost 50% with a highly significant P value. We weren't powered to compare the other arms against each other, but we did, and although it wasn't statistically significant, there was an incremental benefit of the vaccine alone over [BSC], and an incremental benefit for the combination over the vaccine alone.
Patient characteristics were balanced across all arms. Over 50% of patients were [homologous recombination deficiency] positive, half were in complete or partial response to chemotherapy and half had stable disease, and 85% had prior exposure to both a PARP inhibitor and bevacizumab, with the remaining 15% having a contraindication.
