In April 2023 Ultimovacs ASA announced that it has adjusted guidance for communication of top-line data from early 2023 to later in the year. A statement from the company indicated that this was due to slow disease progression in patients. However, it is uncertain to what extent the vaccine was contributing to this delay.
UV1 is a universal cancer vaccine designed to induce a specific T cell response against human telomerase (hTERT). It comprises long, synthetic peptides, which represent a sequence in the reverse transcriptase subunit hTERT, shown to induce CD4+ T cells. These cells can provide inflammatory signals and support believed to be “critical for triggering a strong anti-tumour” response.
Ultimovacs states that, following intradermal injection, antigen presenting cells (APCs) in the skin are exposed to the vaccine peptides. The APCs process the peptides and present vaccine epitopes on Human Leukocyte Antigen (HLA) molecules to naïve T cells in the lymph nodes. Activated vaccine T cells will then enter the circulation and identify cells displaying their cognate antigen in the context of HLA molecules.
The vaccine is administered over 3 months as 8 injections alongside the immune-modulator GM-CSF. It is being investigated in the INITIUM trial, a comparative, randomised Phase II trial for first-line treatment of patients with advanced or metastatic malignant melanoma. Enrolment began in June 2020 and was completed in June 2022 with 156 patients.
An encouraging sign
CEO of Ultimovacs, Dr Carlos de Sousa, is “encouraged”. Disease progression is “slower than anticipated” in comparison with “historical data”.
“This is positive for patients, though we do not know if UV1-related efficacy is responsible for this extended time to expected readout since both Ultimovacs and the investigators remain blinded.”
Dr de Sousa looks forward to “learning to what degree UV1 may have contributed to the clinical outcome for patients”.
INITIUM has an “event-driven design”, resulting in top-line progression free survival results being disclosed after progression or death has been verified in 70 patients. Historical data for a combination of ipilimumab and nivolumab indicated that this progression might occur by the first half of 2023. However, it is taking “longer than anticipated” to observe this progression in the required number of patients. Thus, the top-line results will not be announced before the second half of 2023.