UV1 Cancer Vaccine as a Pembrolizumab Add-On Continues to Strengthen OS in Melanoma

The universal cancer vaccine UV1 added to the PD-1 inhibitor pembrolizumab (Keytruda) elicited sustained overall survival (OS) outcomes as frontline therapy in patients with advanced, unresectable, or metastatic malignant melanoma, according to updated findings from both cohorts of the phase 1 UV1-103 trial (NCT03538314).¹

At a median follow-up of 53.0 months and a minimum follow-up of 4 years, among the 30 patients enrolled in the trial, all patients who were alive at 3 years (69.5%) remained alive at 4 years.

“We are encouraged by the strong OS rate observed in this phase 1 study,” Jens Bjørheim, chief medical officer at Ultimovacs, stated in a news release. “The data show a high survival rate among patients enrolled in the UV1-103 trial, even after a minimum of 4 years of follow-up. We look forward to the readout of the [phase 2] FOCUS trial [NCT05075122] in head and neck cancer, where the same treatment combination has been used.”

UV1 is a therapeutic cancer vaccine that is designed to induce a T-cell response against telomerase. The vaccine is composed of synthetic peptides that appear in a sequence in hTERT, which has been shown to induce CD4-positive T cells that may provide inflammatory signals. Following intradermal injection of UV1, antigen-presenting cells in the skin become exposed to the peptides. The antigen-presenting cells then process the peptides and present vaccine epitopes on human leukocyte antigen (HLA) molecules to naive lymph node T cells. The activated vaccine-specific T cells then enter the circulation and target cells displaying their cognate antigen in the context of HLA molecules.

UV1-301 enrolled 30 patients in the United States across 2 cohorts, which are distinguishable by the concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF) used as a vaccine adjuvant. Patients in cohort 1 (n = 20) received a 37.5 µg adjuvant dose of GN-CSF per UV1 vaccination. Patients in cohort 2 (n = 10) received the standard 75 µg adjuvant dose of GM-CSF per UV1 vaccination. The primary end point of UV1-103 was the frequency and severity of adverse effects.² Key secondary end points included tumor response per RECIST 1.1 and iRECIST criteria, as well as OS.

UV1-103 has met its primary end point of the safety and tolerability of UV1 added to pembrolizumab.1Previously reported data from this trial showed a 33% complete response rate, a 57% objective response rate, and a median progression-free survival of 18.9 months per iRECIST criteria. The respective 12-, 24-, 36-, and 48-month OS rates were 87%, 73%, 69.5%, and 69.5%. Furthermore, findings from biomarker analyses published in October 2022 demonstrated robust clinical responses in patients who received the combination of UV1 and pembrolizumab, regardless of PD-L1 status.

The safety profile of the combination has been shown to be comparable with that of pembrolizumab monotherapy. Nine deaths occurred across both cohorts, 4 of which happened during the first year of treatment. Four deaths occurred during the second year, and 1 happened during the third year.

Three patients enrolled in cohort 1 chose not to be followed beyond 24 months.

In 2021, the FDA granted fast track designation to UV1 as an add-on therapy to either pembrolizumab or ipilimumab (Yervoy) in patients with unresectable or metastatic melanoma.³

The FOCUS trial is evaluating the safety and efficacy of UV1 vaccination as an add-on to pembrolizumab in patients with recurrent or metastatic PD-L1–positive head and neck squamous cell carcinoma.⁴

References

1. 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 June 11, 2024. https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=4657094&lang=en-GB&companycode=no-ulti&v=
2. UV1 vaccine with pembrolizumab for patients with unresectable or metastatic melanoma. ClinicalTrials.gov. Updated November 17, 2022. Accessed June 11, 2024. https://clinicaltrials.gov/study/NCT03538314
3. Ultimovacs receives dual FDA fast track designation for UV1 in advanced malignant melanoma. News release. Ultimovacs ASA. October 21, 2021. Accessed June 11, 2024. https://www.globenewswire.com/news-release/2021/10/21/2317976/0/en/Ultimovacs-Receives-Dual-FDA-Fast-Track-Designation-for-UV1-in-Advanced-Malignant-Melanoma.html
4. 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 June 11, 2024. https://www.clinicaltrials.gov/study/NCT05075122