The long, ever-extending wait for midphase melanoma data is driving Ultimovacs to weigh its options. After slow disease progression drove another delay, the Norwegian biotech revealed it will explore alternative data readout approaches if the event-driven trial continues to advance sluggishly.
Oslo-based Ultimovacs designed the phase 2 INITIUM trial to assess the effect of adding its cancer vaccine candidate UV1 to Bristol Myers Squibb’s checkpoint inhibitors Opdivo and Yervoy. The biotech finished enrolling 156 first-line melanoma patients in July 2022 and, based on historical data on recipients of Opdivo and Yervoy, predicted that 70 people would progress or die by the first half of 2023.
Ultimovacs pushed its target completion date back to the second half of 2023 in April after the tumors of participants in the trial progressed slower than expected. Tuesday, the biotech delayed the readout to the first half of 2024 and revealed that the wait has led it to mull alternative approaches to the data.
Talking to investors on a second-quarter results conference call, Jens Bjørheim, M.D., Ph.D., chief medical officer at Ultimovacs, explained that most of the patients have reached the progression-free survival plateau seen in recipients of checkpoint inhibitors. As such, Ultimovacs expects “slow progression of new events over the next period of time” and is assessing whether it can wrap up the trial before reaching the event threshold.
“We have already started internally to explore alternative approaches for data readout and we will of course, in due time, discuss with regulatory authorities how to proceed with the closing of the database and readout of this trial,” Bjørheim said. “It could be that [the independent data monitoring committee] can also look into efficacy data, but … this has not yet been discussed fully internally.”
Ultimovacs declined to tell investors how close it is to the 70-event threshold that will trigger the primary endpoint analysis, but it is clear patients are staying healthy for much longer than expected. The BMS trials Ultimovacs used to inform its study reported median progression-free survival (PFS) of between 9.5 months and 11.5 months. All patients in INITIUM have been tracked for at least 13 months.
Whether UV1 or another factor is driving the improved PFS is unclear. The candidate is made of three long synthetic peptides that are designed to induce a T-cell response against telomerase, an enzyme that is active in most cancer cells and supports their rapid proliferation. UV1 failed to improve PFS in a phase 2 mesothelioma trial, but Ultimovacs highlighted other evidence as more encouraging.
The biotech’s cash runway extends into the second half of next year. Based on the current timeline, Ultimovacs expects to report data from INITIUM and two other randomized phase 2 trials of UV1 before reaching the end of its runway.