First-Line UV1 Vaccine Plus Pembrolizumab Sustains OS in Unresectable or Metastatic Melanoma

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First-line treatment with the universal cancer vaccine UV1 in combination with pembrolizumab (Keytruda) sustained overall survival (OS) in patients with advanced unresectable or metastatic malignant melanoma, according to updated data from cohort 1 of the phase 1 UV1-103 trial (NCT03538314).¹

Previous data showed that the 3-year OS rate was 70.6% (n = 12/17), and updated findings showed that the 4-year OS rate was 68.8% (n = 11/16). Notably, 1 patient included in the 3-year data could temporarily not be reached, and that patient’s 4-year OS outcome is pending.

The 1-, 2-, 3-, and 4-year OS rates in cohort 1 per absolute numbers were 85.0% (n = 17/20), 80.0% (n = 16/20), 70.6% (n = 12/17), and 68.8% (n = 11/16), respectively. In cohort 2, the 1-, 2-, and 3- year absolute OS rates were 90% (n= 9/10), 60% (n = 6/10), and 60% (n = 6/10), respectively. Across all patients in both cohorts, the 1-, 2-, and 3-year absolute OS rates were 86.7% (n = 26/30), 73.3% (n = 22/30), and 66.7% (n = 18/27), respectively.

Using Kaplan-Meier estimates, the 1-, 2-, 3-, and 4-year OS rates for cohort 1 were 85.0%, 80.0%, 73.8%, and 73.8%, respectively. The 1-, 2-, and 3-year OS rates for cohort 2 were 90%, 60%, and 60%, respectively. In both cohorts, the 1-, 2-, and 3-year OS rates were 86.7%, 73.3%, and 69.5%, respectively.

“We are very encouraged to report a durable and long-term OS rate at the 4-year follow-up in the UV1-103 study. The data further strengthen the previously reported results from the study, including good safety for UV1 and the high number of complete responses in patients with metastatic malignant melanoma where surgery is not an option,” Jens Bjørheim, chief medical officer at Ultimovacs, stated in a news release. “The UV1-103 study treats the same patient population as our phase 2 INITIUM [trial (NCT04382664)]. As we await data from the first three randomized UV1 Phase II trials in the near-term, we are increasingly optimistic about UV1’s potential to benefit cancer patients.”

Previously reported data from cohort 1 (n = 20) and cohort 2 (n = 10) of UV1-103 showed UV1 plus pembrolizumab elicited an objective response rate (ORR) of 57% and a complete response rate of 33%. The median progression-free survival (PFS) was 18.9 months.

UV1-103 was an open-label, multicenter trial that enrolled patients with stage IIIB, IIIC or IV melanoma who were previously untreated and were eligible to receive pembrolizumab. Notably, prior treatment with BRAF and MEK inhibitors was permitted. Patients also needed to have adequate blood, liver, and kidney function.

Patients with uveal or ocular malignant melanoma were excluded. Other key exclusion criteria included prior systemic treatment for unresectable or metastatic melanoma other than BRAF/MEK inhibitors; prior therapy with an anti–CTLA-4, anti–PD-1, anti–PD-L1, or anti–PD-L2 agents or an oncolytic virus; and a known hypersensitivity to granulocyte-macrophage colony–stimulating factor (GM-CSF).

Patients in cohort 1 received adjuvant GM-CSF at 37.5 µg per UV1 vaccination. In cohort 2, adjuvant GM-CSF was given at 75 µg per UV1 vaccination.¹

The trial had previously reached its primary end point of safety and tolerability, and no unexpected safety signals related to UV1 were reported.

Data for 4-year OS rates across both cohorts of UV1-103 are expected to be reported in the second quarter of 2024.

INITIUM is evaluating UV1 in combination with ipilimumab (Yervoy) and nivolumab (Opdivo) in patients with advanced unresectable or metastatic malignant melanoma, and it completed enrollment with 156 patients in July 2022. Data are expected to read out in the first half of 2024.

References

1. Ultimovacs provides 4-year update from phase I study in malignant melanoma: demonstrating sustained long-term overall survival in patients treated with UV1 cancer vaccine. News release. Ultimovacs. October 12, 2023. Accessed October 12, 2023. https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=4389875&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 October 12, 2023. https://clinicaltrials.gov/study/NCT03538314