Adding UV1 Vaccine to Olaparib/Durvalumab Maintenance Misses PFS End Point in BRCA-Wild Type Recurrent Ovarian Cancer

The addition of the therapeutic cancer vaccine UV1 to maintenance olaparib (Lynparza) plus durvalumab (Imfinzi) did not significantly improve progression-free survival (PFS) vs olaparib alone in patients with BRCA-wild type recurrent ovarian cancer, according to first results from the phase 2 ENGOT-OV56/NSGO-CTU-DOVACC trial (NCT04742075) presented at the 2026 ESMO Congress.¹ However, exploratory subgroup analyses suggested a possible signal of benefit with the triplet in patients with homologous recombination deficiency (HRD)–negative disease and in those who had not previously received a PARP inhibitor.

At a median follow-up of 22.6 months (95% CI, 19.5-28.1), the median PFS was 8.7 months (95% CI, 6.1-11.3) with olaparib, durvalumab, and UV1 (arm C; n = 94) vs 5.9 months (95% CI, 5.3-8.2) with olaparib alone (arm A; n = 46; HR, 0.83; 95% CI, 0.68-1.01; 2-sided P = .066). PFS events had occurred in 64 patients (68%) in arm C and 34 patients (74%) in arm A. Olaparib plus durvalumab (arm B) was given to 48 patients.

"In BRCA wild-type recurrent ovarian cancer, adding UV1 to PARP inhibition with or without durvalumab maintenance did not significantly improve PFS at the 2-sided 0.05 level," said presenting author Trine Jakobi Nøttrup, MD, PhD, of the Nordic Society of Gynaecological Oncology–Clinical Trial Unit (NSGO-CTU) and Rigshospitalet, Copenhagen University Hospital, in Denmark.

How was the trial designed?

DOVACC is an open-label, 3-arm, randomized phase 2 trial that asked whether immune activation with UV1, a therapeutic cancer vaccine directed against human telomerase reverse transcriptase (hTERT), could increase the efficacy of maintenance olaparib with or without durvalumab in BRCA-wild type recurrent ovarian cancer.

Eligible patients had recurrent, BRCA tumor wild-type or non-germline BRCA-mutant ovarian cancer; had completed 2 or 3 prior lines of chemotherapy, with or without bevacizumab (Avastin); and had no disease progression on or after their most recent platinum-based regimen. Prior PARP inhibitor therapy was permitted if it had been given for more than 6 months without progression; prior immunotherapy was not allowed.

A total of 188 patients from 27 sites were randomly assigned 1:1:2 between November 23, 2021, and May 8, 2025, with stratification by HRD status and prior PARP inhibitor use. Olaparib was given at 300 mg orally twice daily for up to 3 years, durvalumab at 1500 mg intravenously every 4 weeks for up to 2 years, and UV1 as 8 intradermal vaccinations over 5 months (4 by day 10, then every 4 weeks). The primary end point was PFS in arm C vs arm A.

Mean ages were 64 years (range, 36-82) in arm A, 64 years (range, 36-85) in arm B, and 65 years (range, 39-84) in arm C. Rates of prior PARP inhibitor exposure were 17%, 21%, and 17%, respectively, and HRD-positive disease was present in 26%, 29%, and 26%. The data cutoff was May 22, 2026.

What did the secondary and subgroup analyses show?

In a post hoc analysis adjusted for HRD status and prior PARP inhibitor use, restricted mean survival time at 22 months showed a 2.5-month difference favoring arm C over arm A (95% CI, 0.1-4.9; exploratory P = .043).

In the secondary comparison of arm C vs arm B, the median PFS with olaparib plus durvalumab was 7.4 months (95% CI, 5.5-8.6; HR, 0.77; 95% CI, 0.51-1.14), with PFS events in 37 patients (77%) in arm B.

In subgroup analyses of arm C vs arm A, the HR for PFS was 0.73 (95% CI, 0.58-0.92) in patients with HRD-negative disease (n = 104) and 1.19 (95% CI, 0.74-1.89) in those with HRD-positive disease (n = 36). The HR was 0.81 (95% CI, 0.65-1.01) in patients without prior PARP inhibitor exposure (n = 116) and 0.95 (95% CI, 0.58-1.54) in those with prior PARP inhibitor exposure (n = 24).

What did the safety analysis show?

The safety population included 45 patients in arm A, 46 in arm B, and 92 in arm C; 5 patients who received no treatment were excluded. Median treatment durations were 5.7 months (range, 1.0-27.8), 7.4 months (range, 1.6-36.2), and 8.3 months (range, 0.5-36.1), respectively.

Adverse effects (AEs) of any grade occurred in 89%, 100%, and 99% of patients in arms A, B, and C, respectively. Grade 3/4 AEs occurred in 16%, 48%, and 39%, and serious AEs in 11%, 50%, and 49%; no grade 5 AEs were reported. The most common grade 3/4 AE was anemia across arms (11%, 7%, and 10%, respectively); in arm C, decreased neutrophil count (8%), decreased white blood cell count (5%), and decreased platelet count (5%) were also reported.

Olaparib was interrupted in 36%, 52%, and 50% of patients and dose reduced in 24%, 43%, and 47%, respectively. Durvalumab was interrupted in no patients in arm B and 4% of patients in arm C, and at least 1 UV1 dose was omitted in 11% of patients in arm C.

Compared with olaparib alone, both durvalumab-containing arms were associated with increased toxicity. Adding UV1 to durvalumab plus olaparib increased only vaccination complications, headache, and flu-like symptoms.

What are the next steps for DOVACC?

Although DOVACC did not meet its primary end point, the investigators concluded that the subgroup signal in HRD-negative and PARP inhibitor–naive disease warrants further evaluation of cancer vaccines in ovarian cancer. Translational research using tissue and blood samples collected from patients in the academic trial is planned to investigate additional treatment outcome measures, resistance mechanisms, and patient selection.

Other vaccine-based maintenance strategies are also under study in this setting. In the phase 2 GINECO-OV244b/ENGOT-ov58/TEDOVA trial (NCT04713514), the neo-epitope vaccine OSE2101 plus pembrolizumab (Keytruda) improved PFS vs best supportive care as maintenance therapy in patients with platinum-sensitive ovarian cancer previously treated with a PARP inhibitor and bevacizumab.²

References

1. Nøttrup TJ, Lindemann K, Heitz F, et al. First results from the randomised ENGOT-OV56/NSGO-CTU-DOVACC trial investigating olaparib, durvalumab and UV1 vaccination as maintenance therapy for patients with BRCA-wildtype recurrent ovarian cancer. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA39.
2. OSE2101 plus pembrolizumab as maintenance boosts PFS in platinum-sensitive ovarian cancer. OncLive. Published September 15, 2026. Accessed October 23, 2026. https://www.onclive.com/view/ose2101-plus-pembrolizumab-as-maintenance-boosts-pfs-in-platinum-sensitive-ovarian-cancer