OSE2101 Plus Pembrolizumab as Maintenance Boosts PFS in Platinum-Sensitive Ovarian Cancer

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 bevacizumab currently 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 American Society of Clinical Oncology 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 the deputy head of the Department of Medical Oncology and 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?

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, over 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; all have been negative.

Anti–PD-1s alone haven't provided the answer, so we were interested in a different strategy, which led us to investigate 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 the immune checkpoint inhibitor pembrolizumab as maintenance therapy 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 nonmucinous histology 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 randomly assigned 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 end point 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.

What was the safety profile of the OSE2101 vaccine? What measures were taken to address any select toxicities?

In terms of [tolerability], we saw a numerical increase in immune-related toxicity in the combination arm, mainly grade 1/2. The most common event was injection site reaction, but the more intriguing finding was cytokine release syndrome [CRS]. CRS doesn't typically occur with pembrolizumab alone and is very rare with the vaccine alone; we saw a 9% incidence with the vaccine alone, mainly grade 1/2, but almost 30% with the combination. During the trial, we thought this was an encouraging finding because it suggested some kind of synergy between the vaccine and pembrolizumab, and that we were clearly stimulating the immune system. Halfway through the trial, we introduced basic primary prophylaxis with paracetamol and [nonsteroidal anti-inflammatory drugs] to try to prevent some of these CRS events, and that nicely decreased the incidence of grade 1/2 CRS.

Are there any lingering questions or concerns with the vaccine approach you'd like to explore further?

CRS prophylaxis, which we hadn't [considered] at the beginning of the study, is clearly something we should implement. Early in the study, CRS caused investigators to stop [treatment prematurely], and in the subgroup analysis, you can see that patients who received primary prophylaxis did better, probably because they stayed on vaccine and pembrolizumab longer. That's an important message for managing toxicity in gynecologic oncology.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

References

1. Leary A, Van Gorp T, Marmé F, et al. The neo-epitope-based vaccine OSE2101 with or without pembrolizumab versus best supportive care as maintenance in platinum-sensitive recurrent ovarian cancer patients with controlled disease after platinum-based chemotherapy: the academic randomized TEDOVA/GINECO-OV244b/ENGOT-ov58 trial. J Clin Oncol. 2026;44(suppl 16):5510. doi:10.1200/JCO.2026.44.16_suppl.5510
2. Kurtz JE, Pujade-Lauraine E, Oaknin A, et al; ATALANTE/ENGOT-ov29 Investigators. Atezolizumab combined with bevacizumab and platinum-based therapy for platinum-sensitive ovarian cancer: placebo-controlled randomized phase III ATALANTE/ENGOT-ov29 trial. J Clin Oncol. 2023;41(30):4768-4778. doi:10.1200/JCO.23.00529
3. Harter P, Marth C, Mouret-Reynier MA, et al; PAOLA-1/ENGOT-ov25 investigators. Efficacy of subsequent therapies in patients with advanced ovarian cancer who relapse after first-line olaparib maintenance: results of the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2025;36(2):185-196. doi:10.1016/j.annonc.2024.10.828