FDA Grants Fast Track Designation to UV1 Vaccine Combo in Unresectable Mesothelioma

Supporting data for the designation came from the phase 2 Nivolumab and Ipilimumab Plus/minus UV1 vaccination (NIPU) trial (NCT04300244).

The FDA has granted fast track designation to UV1, an investigational cancer vaccine, plus nivolumab (Opdivo) and ipilimumab (Yervoy) in the management of unresectable malignant pleural mesothelioma, according to a press release from Ultimovacs ASA, the developer of the vaccine.¹

The indication includes the vaccine-based combination as a treatment for those in the first-line setting. Supporting data for the designation came from the phase 2 Nivolumab and Ipilimumab Plus/minus UV1 vaccination (NIPU) trial (NCT04300244).

“We are pleased that the FDA has granted fast track designation for UV1 in 2 separate advanced indications, which underlines the potential of our cancer vaccine approach,” Carlos de Sousa, chief executive officer at Ultimovacs said in the press release. “UV1 demonstrated a positive safety profile and encouraging signs of improvement in overall survival [OS] in combination with the checkpoint inhibitors, ipilimumab, and nivolumab, in malignant mesothelioma, a hard-to-treat cancer indication with significant unmet need. We expect to announce topline results from our randomized phase 2 trial INITIUM in the coming month of March, and we are looking forward to reporting important data from our broad UV1 phase 2 clinical trial program with UV1 over the course of 2024 and beyond.”

Findings from the NIPU trial were presented as part of a late-breaking abstract at the 2023 European Society for Medical Oncology Congress (ESMO). With a median follow-up of 17.3 months (95% CI, 15.8-22.9), the median OS with UV1 plus nivolumab and ipilimumab in arm A was 15.4 months (95% CI, 11.1-22.6) compared with 11.1 months (95% CI, 8.8-18.1) with nivolumab/ipilimumab alone in arm B (HR, 0.73; 80% CI, 0.53-1.00; 95% CI, 0.45-1.18).² The OS improvement observed with the vaccine-based combination was found to be statistically significant.

Treatment in arm A produced a median progression-free survival (PFS) of 4.2 months (95% CI, 2.9-9.8) vs 4.7 months (95% CI, 3.9-7.0) in arm B based on blinded independent central review (BICR; HR, 1.01; 80% CI, 0.75-1.36; 95% CI, 0.64-1.59). The median PFS in each respective arm based on investigator assessment was 4.3 months (95% CI, 3.0-6.8) vs 2.9 months (95% CI, 2.4-5.5; HR, 0.60; 80% CI, 0.45-0.81; 95% CI, 0.39-0.94). Further data highlighted an objective response rate (ORR) of 31% and 16% in each respective arm (OR, 2.4; 95% CI, 1.0-6.3).

Investigators reported that the rates of any-grade and grade 3 or higher adverse effects were comparable between the treatment arms.

“The results from the first randomized UV1 phase 2 trial, NIPU…is a proof of concept for UV1,” de Sousa said in a press release on these data.³ “These data reaffirm our unwavering commitment to developing UV1 as an effective add-on treatment to checkpoint inhibitors for a range of cancers. We eagerly anticipate the forthcoming results from our other ongoing phase 2 trials and how these data will move us forward in our mission to improve outcomes for [patients with] cancer worldwide.”

In the NIPU trial, 118 patients with malignant pleural mesothelioma were randomly assigned 1:1 to receive nivolumab at 240 mg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks with or without 8 intradermal injections of UV1 during the first 3 months of study treatment. The trial’s primary end point was BICR-assessed PFS.

The FDA previously granted orphan drug designation to UV1 as a treatment for those with mesothelioma based on findings from the NIPU trial in October 2023.⁴

References

1. Ultimovacs receives FDA fast track designation for UV1 cancer vaccine for the treatment of patients with unresectable mesothelioma. News release. Ultimovacs ASA. February 5, 2024. Accessed February 6, 2024. http://tinyurl.com/8za87vvc
2. Helland A, Haakensen VD, Ojlert AK, et al. First survival data from the NIPU trial: A randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second-line treatment in patients with malignant mesothelioma. Ann Oncol. 2023;34 (suppl 2):S1337. doi:10.1016/j.annonc.2023.10.102
3. Ultimovacs provides complete phase II NIPU results presented at ESMO 2023: significant and clinically meaningful improvement in overall survival for patients with malignant mesothelioma receiving UV1 cancer vaccine. News release. Ultimovacs ASA. October 23, 2023. Accessed February 6, 2024. http://tinyurl.com/3fuemj4x
4. Ultimovacs receives FDA orphan drug designation for the UV1 cancer vaccine for treatment of mesothelioma. News release. Ultimovacs ASA. October 9, 2023. Accessed February 6, 2024. http://tinyurl.com/2kecjkbt