Ultimovacs updates on Phase I melanoma study: Strong survival with UV1 vaccine and pembrolizumab

Ultimovacs ASA, a clinical-stage biotechnology firm focused on developing immunotherapeutic cancer vaccines, has unveiled promising overall survival (OS) data from its UV1-103 Phase I clinical trial in treating malignant melanoma. This announcement, made on June 11, 2024, highlights notable progress in their research.

The UV1-103 study investigates the efficacy of Ultimovacs’ universal cancer vaccine, UV1, combined with the anti-PD-1 checkpoint inhibitor pembrolizumab, as a first-line treatment for patients with advanced, non-resectable, or metastatic malignant melanoma. The trial involved 30 U.S.-based patients divided into two cohorts, differentiated only by the concentration of GM-CSF used as a vaccine adjuvant.

After a minimum follow-up period of 4 years (median 53.0 months), the updated OS results are remarkable. All patients alive at the 3-year mark remained alive at the 4-year mark, reflecting an OS rate of 69.5%. This data suggests a sustained benefit from the combination treatment over an extended period.

Previously reported data from the UV1-103 study showed a complete response rate of 33% and an objective response rate of 57%, indicating significant tumor reduction or disappearance in many patients. Further biomarker analyses in October 2022 confirmed that the combination treatment elicited strong clinical responses irrespective of the patients’ PD-L1 status. Additionally, the safety profile of UV1 in conjunction with pembrolizumab mirrors that of pembrolizumab on its own, reinforcing the combination's safety.

Chief Medical Officer Jens Bjørheim expressed optimism about these findings, highlighting the high survival rate among trial participants even after four years of follow-up. He also looked forward to the outcomes of the upcoming FOCUS trial in head and neck cancer, which employs the same treatment regimen as the UV1-103 trial.

The UV1-103 Phase I trial, which has now completed its enrollment, evaluated 30 patients in two cohorts receiving different doses of the GM-CSF adjuvant. One cohort received a 37.5 mcg GM-CSF dose per vaccination, while the other received a 75 mcg dose. The trial met its primary endpoints of safety and tolerability, with no unexpected safety issues related to UV1 observed.

The compiled clinical outcomes for the 30 patients are as follows:
- Objective response rate (ORR): 57%
- Complete response rate (CR): 33%
- Median Progression-Free Survival (mPFS): 18.9 months

Overall survival rates recorded were:
- 87% at 12 months
- 73% at 24 months
- 69.5% at both 36 and 48 months

Of the nine recorded deaths, four occurred within the first year, another four in the second year, and one in the third year across both cohorts. Notably, three patients from the first cohort opted out of follow-up beyond 24 months.

Historically, the registrational study for pembrolizumab (Keynote-006) demonstrated an overall survival rate of 42% at 48 months, underscoring the promising results observed in the UV1-103 study.

The U.S. FDA has granted UV1 in combination with checkpoint inhibitors a dual Fast Track designation for treating unresectable or metastatic melanoma, either as an add-on to pembrolizumab or ipilimumab. Ultimovacs continues to pioneer in the field of cancer vaccines, with their lead candidate UV1 showing significant potential across multiple cancer types. With ongoing Phase II trials encompassing over 670 patients and various cancer indications, the company aims to further validate UV1’s efficacy in combination with other immunotherapies.

UV1 is designed to trigger a specific T-cell response against telomerase, an antigen prevalent in 85-90% of cancers. Following intradermal injection, UV1 prompts the immune system to target cancer cells, leveraging its unique composition of synthetic peptides to stimulate a robust anti-tumor response. The vaccine’s broad applicability, without the need for HLA pre-screening, holds promise for widespread use across diverse patient populations.