UV1 Vaccine Data Keep hTERT in Focus as an Immunotherapy Target in Recurrent Ovarian Cancer

The therapeutic cancer vaccine UV1, which targets human telomerase reverse transcriptase (hTERT), did not significantly improve progression-free survival (PFS) when added to olaparib (Lynparza) and durvalumab (Imfinzi) as maintenance therapy in patients with BRCA wild-type recurrent ovarian cancer in the phase 2 DOVACC trial (NCT04742075). However, exploratory subgroup analyses suggested that patients with homologous recombination deficiency (HRD)–negative or PARP inhibitor–naive disease could derive benefit, keeping hTERT under investigation as an immunotherapy target in this population.^1,2

Findings from DOVACC presented at the 2026 ESMO Congress showed that 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).²

"We did see an improvement in PFS from 5.9 months to 8.7 months, but unfortunately, it was not quite statistically significant," lead study author Trine Jakobi Nøttrup, MD, PhD, said in an interview with OncLive®. "[However], this is clinically meaningful, especially when we look into the subgroups."

Nøttrup is the lead principal investigator of DOVACC and is based at Rigshospitalet, Copenhagen University Hospital, in Denmark. She is also president of the Nordic Society of Gynaecological Oncology (NSGO), whose clinical trials unit led the study.

What Is hTERT, and why target it with a vaccine?

Telomerase is activated in approximately 85% to 90% of all cancers, where it enables unlimited cellular proliferation and increases metastatic potential, making its catalytic subunit, hTERT, a potential near pan-tumor antigen for immunotherapy.² High telomerase activity is a negative prognostic factor across several malignancies, whereas spontaneous immune responses against hTERT have been associated with improved outcomes in several tumor types.

UV1 is a second-generation telomerase-targeting vaccine consisting of 3 synthetic long peptides derived from a clinically validated immunogenic region of the hTERT active site. Because these long peptides require intracellular processing, they are presented on human leukocyte antigen (HLA) class II molecules to stimulate CD4-positive T helper 1 cells and on HLA class I molecules via cross-presentation to stimulate CD8-positive T cells.

Researchers selected the active site in part to limit tumor escape, because mutations in these epitopes would likely impair telomerase activity and, in turn, tumor growth. The peptide pool was also designed to match a broad range of HLA types, so patients do not need to be selected by HLA genotype.

UV1 was previously evaluated in 3 phase 1/2a trials enrolling patients with melanoma (NCT02275416), non–small cell lung cancer (NCT01789099) or prostate cancer (NCT01784913), in which the vaccine was generally safe and induced measurable hTERT-specific immune responses in most patients, some lasting years after the final dose. Responses developed more rapidly and frequently when UV1 was combined with the checkpoint inhibitor ipilimumab (Yervoy), and the investigators concluded that the data supported randomized trials pairing UV1 with checkpoint blockade, including the combination with durvalumab in ovarian cancer that became DOVACC.

What was the rationale for the DOVACC trial?

PARP inhibitor maintenance after response to platinum-based chemotherapy is a standard approach in recurrent ovarian cancer, but outcomes are more limited in patients without BRCA alterations, particularly those with HRD-negative tumors.

DOVACC was designed to test whether immune activation with an hTERT-directed vaccine could increase the efficacy of maintenance olaparib with or without durvalumab in this setting.^1,3

"[In this trial], we wanted to see if we could improve the PFS of patients with recurrent ovarian cancer after platinum treatment," Nøttrup said.

The open-label study enrolled patients with non-germline BRCA-mutated or tumor BRCA wild-type recurrent ovarian cancer who had completed 2 to 3 prior lines of chemotherapy, with or without bevacizumab (Avastin), without disease progression on or after the most recent platinum-based regimen.¹ Prior PARP inhibitor therapy was permitted if it had been given for more than 6 months without progression, and prior immunotherapy was not allowed.

Patients were randomly assigned 1:1:2 to receive olaparib at 300 mg orally twice daily for up to 3 years (arm A); olaparib plus durvalumab at 1500 mg intravenously every 4 weeks for up to 2 years (arm B; n = 48); or olaparib, durvalumab, and UV1 (arm C). UV1 was administered as 8 intradermal vaccinations over 5 months, with 4 given by day 10 and the remainder every 4 weeks.

Randomization was stratified by HRD status and prior PARP inhibitor use. The primary end point was PFS in arm C vs arm A, and PFS in arm C vs arm B was a secondary end point.

What other data did DOVACC show?

A total of 188 patients from 27 sites were randomly assigned between November 23, 2021, and May 8, 2025. Across arms, 17% to 21% of patients had received a prior PARP inhibitor, and 26% to 29% had HRD-positive disease.

In a post hoc restricted mean survival time analysis at 22 months adjusted for HRD status and prior PARP inhibitor use, PFS was 2.5 months longer in arm C vs arm A (95% CI, 0.1-4.9; exploratory P = .043). For the secondary end point of PFS for the UV1 regimen vs olaparib plus durvalumab alone, the median PFS was 8.7 months in arm C vs 7.4 months (95% CI, 5.5-8.6) in arm B (HR, 0.77; 95% CI, 0.51-1.14).

Regarding safety, grade 3/4 adverse effects (AEs) occurred in 16% of patients in arm A, 48% of patients in arm B, and 39% of patients in arm C; no grade 5 AEs were reported. Serious AEs occurred at rates of 11%, 50%, and 49%, respectively. Anemia was the most common grade 3/4 AE in all arms. Compared with olaparib plus durvalumab, the addition of UV1 increased only vaccination complications, headache, and flu-like symptoms. UV1 was omitted for at least 1 dose in 11% of patients in arm C.

"The vaccine AEs were related to the [initial] period of the study, where [patients] did receive the vaccines, and that was over the first 5 months," Nøttrup said. "After that, there were no vaccine-related AEs."

She added that fatigue, a common concern with any maintenance therapy, was attributable to olaparib and durvalumab rather than the vaccine, and that immune-related AEs with the combination were comparable with those seen with other checkpoint inhibitor–based regimens.

Which patients may benefit from hTERT-directed vaccination?

In exploratory 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 0.81 (95% CI, 0.65-1.01) in those without prior PARP inhibitor exposure (n = 116). No benefit was observed in patients with HRD-positive disease (n = 36; HR, 1.19; 95% CI, 0.74-1.89) or in those previously treated with a PARP inhibitor (n = 24; HR, 0.95; 95% CI, 0.58-1.54). In a pooled analysis of all arms, PFS was significantly better in PARP inhibitor–naive vs PARP inhibitor–exposed patients (HR, 0.55; 95% CI, 0.37-0.83; exploratory P = .004).¹

"[Efficacy] seems to be biomarker-driven, but the trial was not [designed] to show that definitively," Nøttrup explained. "It seems that the patients who were HRD positive and the ones who had [received a PARP inhibitor] before did not benefit from a vaccine. However, we still don't know if being HRD negative or not having prior PARP [inhibitor therapy are] the 2 strongest biomarkers for effect. We need to investigate that further."

What are the next steps for hTERT vaccination?

Investigators concluded that the subgroup signals warrant further evaluation of cancer vaccines in ovarian cancer. Translational research is planned using the trial's collection of tissue and blood samples to investigate additional treatment outcome measures, resistance mechanisms, and patient selection.¹

"The study did show that some groups of patients might benefit from a vaccine, but unfortunately, we cannot say that for sure yet," Nøttrup said. "That encouraged us to look more into the data to see if we, in the future, can design a better trial to find a way to make vaccines work for patients with ovarian cancer."

She noted that the planned translational work will focus on the immune system and the tumor microenvironment to determine whether any subgroups can be selected for further investigation. Patient-reported outcomes and time to subsequent treatment, both secondary end points, are also being analyzed for inclusion in the first publication of the trial.

"The effort that the patients have to put into this is quite little compared with what benefit they can get out," Nøttrup concluded. "We are very eager to see if we can find companies out there who will work with us to go further with vaccine treatment for certain types of patients with ovarian cancer."

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. Ellingsen EB, Aamdal E, Guren T, et al. Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials. J Immunother Cancer. 2022;10(5):e004345. doi:10.1136/jitc-2021-004345
3. A randomized clinical trial investigating olaparib, durvalumab (MEDI4736) and UV1 as maintenance therapy in BRCAwt patients with recurrent ovarian cancer (DOVACC). ClinicalTrials.gov. Accessed November 5, 2026. https://clinicaltrials.gov/study/NCT04742075