UV1 Vaccination Plus Nivolumab/Ipilimumab Falls Short in Metastatic Melanoma

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The addition of the universal cancer vaccine UV1 to the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) did not improve progression-free survival (PFS) compared with nivolumab plus ipilimumab alone in the first-line treatment of patients with unresectable or metastatic melanoma, failing to meet the primary end point of the phase 2 INITIUM trial (NCT04382664).¹

Topline findings showed that at a minimum follow-up of 18 months, the median PFS was not reached in either arm (HR, 0.95). Furthermore, differences in overall survival (OS) and overall response rate (ORR) were not observed between the 2 arms.

“Ultimovacs had set a very high bar for UV1 by comparing it to the ipilimumab and nivolumab combination, currently considered the most effective treatment for this patient population. Nevertheless, we are disappointed that UV1 did not add further clinical benefit for these [patients with] late-stage melanoma in the INITIUM trial. Looking forward, our first objective is to complete the analysis of the full data set in depth to gain further insights on UV1’s effects,” Jens Bjørheim, chief medical officer of Ultimovacs, stated in a news release. “We wish to thank the patients for their trust and the investigators for their collaboration with us.”

UV1 is designed to induce a specific T-cell response against telomerase. The vaccine features long, synthetic peptides representative of a sequence in the reverse transcriptase subunit of telomerase, which has shown to induce CD4-positive T-cells.

The phase 2 INITIUM trial enrolled 156 patients at least 18 years of age with a histologically confirmed diagnosis of unresectable stage IIIB to IIID, or unresectable stage IV malignant melanoma.^1,2 Patients must have been eligible to receive combination treatment with nivolumab and ipilimumab, have an ECOG performance status of 0 or 1, and have adequate organ function.²

Patients could not have had a previous non-melanoma malignancy, unless it was curatively treated and complete remission was achieved at least 2 years prior to randomization. Other exclusion criteria included having known brain metastases or leptomeningeal metastases, uveal or ocular melanoma, or prior receipt of systemic treatment for unresectable stage IIIB to IIID or unresectable stage IV malignant melanoma.

Patients were randomly assigned to receive standard-of-care nivolumab plus ipilimumab with or without UV1. Those in the experimental arm received intradermal UV1 at 300 µg, and sargramostim was given at 75 µg as a vaccine adjuvant.

Along with the primary end point of PFS per RECIST v1.1 criteria, secondary end points included OS, ORR, duration of response, and safety.

UV1 maintained a positive safety and tolerability profile.

“We have seen signals in previous trials that UV1 has the ability to show positive effects in [patients with] cancer,” Carlos de Sousa, chief executive officer of Ultimovacs, added in the news release. “We remain committed to UV1, and we look forward to thoroughly examining the INITIUM data, receiving the FOCUS data, and updated NIPU survival data over the next several months. Our objective is to define the best path forward for our development strategy for UV1.”

References

1. 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 March 7, 2024. https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=4475644&lang=en-GB&companycode=no-ulti&v=
2. UV1 vaccination plus nivolumab and ipilimumab in treatment of melanoma. ClinicalTrials.gov. Updated December 27, 2023. Accessed March 7, 2024. https://www.clinicaltrials.gov/study/NCT04382664