UV1 Plus Pembrolizumab Fails to Yield Survival Benefit in Metastatic/Recurrent Head and Neck Cancer

The addition of UV1 to pembrolizumab (Keytruda) did not lead to an improvement in progression-free survival (PFS) or overall survival (OS) vs pembrolizumab alone as frontline therapy in patients with metastatic head and neck cancer nor as second-line therapy in those with recurrent PD-L1–positive disease, failing to meet the primary and secondary end points of the investigator-initiated phase 2 FOCUS trial (NCT05075122).¹

The announcement comes months after the company announced that the agent failed to demonstrate a PFS benefit in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) vs nivolumab plus ipilimumab alone as frontline therapy in patients with unresectable or metastatic melanoma.² Despite the negative results from the phase 2 INITIUM trial (NCT04382664), the agent upheld OS outcomes in combination with pembrolizumab in the same population in the phase 1 UV1-103 trial (NCT03538314).³

“We have implemented a broad phase 2 clinical development program testing our cancer vaccine in a range of different indications. Unfortunately, the FOCUS study did not provide us with the results we had hoped for, and we are disappointed that UV1 was not able to provide added clinical benefit for these head and neck squamous cell carcinoma [HNSCC] patients,” Carlos de Sousa, chief executive officer at Ultimovacs, stated in a news release.¹ “Earlier this year we implemented a cash preservation program, enabling us to extend our runway to the fourth quarter of 2025 beyond the anticipated DOVACC [NCT04742075] phase 2 topline readout in the first half of next year. Further, the Ultimovacs team is actively developing a novel technology platform identified during the TET development, and we look forward to providing more details before year-end.”

UV1 is a therapeutic cancer vaccine designed to create a T-cell response against telomerase 1 that received fast track designation from the FDA as an add-on therapy in combination with ipilimumab and nivolumab for the treatment of patients with unresectable malignant pleural mesothelioma.⁴

FOCUS is a randomized, open-label trial open at 10 sites in Germany investigating the agent’s efficacy in patients with head and neck cancer.¹ To be eligible for enrollment, patients had to have received a histologically confirmed diagnosis of nonresectable recurrent or metastatic HNSCC with at least 1 measurable lesion per RECIST v1.1 criteria. Patients also had to be eligible to receive pembrolizumab and have an ECOG performance status between 0 and 2.⁵

The first patient was enrolled in August 2021. Eligible patients were randomly assigned 2:1 such that 50 patients received UV1 plus pembrolizumab and 25 patients received pembrolizumab alone.¹ In both arms, 200 mg of pembrolizumab was administered intravenously as a flat dose every 3 weeks. In the investigational arm, patients also received 300 μg of UV1 administered in 3 vaccinations the week before starting pembrolizumab, followed by 5 additional vaccinations on day 1 of each 3-week cycle. The granulocyte macrophage colony-stimulating factor sargramostim was also administered at 75 μg in conjunction with UV1 vaccination.⁵

The primary end point of the trial was the 6-month PFS rate. Secondary end points included PFS and OS, objective response rate, duration of response, and safety, all with a minimum follow-up of 12 months.¹

“We are disappointed that the FOCUS trial did not achieve the desired outcome for patients, which underscores the complexities of treating metastatic and recurrent head and neck cancer. This cancer type is particularly aggressive with limited treatment options and high rates of recurrence. Our broad clinical development program was designed to identify the best patient populations for UV1, and we are now focusing our efforts on the upcoming DOVACC data readout in the first half of next year,” Jens Bjørheim, chief medical officer at Ultimovacs, stated in the news release.

DOVACC is an ongoing phase 2 trial evaluating the combination of olaparib (Lynparza) and durvalumab (Imfinzi) with or without UV1 vs olaparib alone as second-line maintenance therapy in patients with high-grade BRCA-negative ovarian cancer. Topline data from the trial are anticipated in the first half of 2025.

References

1. Ultimovacs announces topline data from FOCUS phase II trial of UV1 combined with pembrolizumab in patients with metastatic or recurrent head and neck cancer. News release. Ultimovacs ASA. August 5, 2024. Accessed August 5, 2024. https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=5738937&lang=en-GB&companycode=no-ulti&v=
2. Ultimovacs announces topline results from INITIUM study evaluating UV1 vaccination added to ipilimumab and nivolumab in patients with unresectable or metastatic malignant melanoma. News release. Ultimovacs. March 7, 2024. Accessed August 5, 2024. https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=4475644&lang=en-GB&companycode=no-ulti&v=
3. Ultimovacs provides update from phase I study in malignant melanoma: continued strong overall survival in patients treated with UV1 cancer vaccine and pembrolizumab. News release. Ultimovacs ASA. June 11, 2024. Accessed August 5, 2024. https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=4657094&lang=en-GB&companycode=no-ulti&v=
4. Ultimovacs receives FDA fast track designation for UV1 cancer vaccine for the treatment of patients with unresectable mesothelioma. News release. Ultimovacs. February 5, 2024. Accessed August 5, 2024. https://ultimovacs.com/investors/news/ultimovacs-receives-fda-fast-track-designation-for-uv1-cancer-vaccine-for-the-treatment-of-patients-with-unresectable-mesothelioma
5. Tolerability and efficacy of UV1 vaccine in patients with recurrent or metastatic head and neck squamous cell carcinoma planned for first-line treatment with pembrolizumab (FOCUS). ClinicalTrials.gov. Updated March 9, 2022. Accessed August 5, 2024. https://www.clinicaltrials.gov/study/NCT05075122