Phase II NIPU Trial Data Lead to FDA Fast Track Designation for Cancer Vaccine in Mesothelioma Treatment

Mesothelial cells in body fluid sample. Image credit: toeytoey | stock.adobe.com

The FDA has granted Fast Track Designation to Ultimovacs ASA’s novel cancer vaccine UV1, which is under evaluation in combination with the checkpoint inhibitors ipilimumab (Yervoy) and nivolumab (Opdivo) to improve overall survival (OS) in patients with unresectable malignant pleural mesothelioma (MPM), including in the first-line setting.¹ The regulatory action was based on data from the Phase II Nivolumab and Ipilimumab Plus/minus UV1 vaccination (NIPU) clinical trial (NCT04300244), presented at the 2023 European Society for Medical Oncology (ESMO).²

“We are pleased that the FDA has granted Fast Track designation for UV1 in two separate advanced indications, which underlines the potential of our cancer vaccine approach. UV1 demonstrated a positive safety profile and encouraging signs of improvement in overall survival in combination with the checkpoint inhibitors, ipilimumab, and nivolumab, in malignant mesothelioma, a hard-to-treat cancer indication with significant unmet need,” said Carlos de Sousa, CEO of Ultimovacs, in a press release. “We expect to announce topline results from our randomized Phase II trial INITIUM in the coming month of March, and we are looking forward to reporting important data from our broad UV1 Phase II clinical trial program with UV1 over the course of 2024 and beyond.”¹

UV1 is an off-the-shelf vaccine that was developed to produce a specific T cell response that acts against telomerase. Findings from the NIPU trial presented at ESMO showed that UV1 plus Yervoy and Opdivo produced a statistically significant and clinically meaningful OS improvement compared with Yervoy and Opdivo alone, which was a key secondary endpoint of the study.²

The randomized, multi-center NIPU trial evaluated UV1 plus Yervoy and Opdivo in the second-line treatment of MPM. Investigators randomly assigned 118 patients 1:1 to either of two cohorts, with all patients administered Opdivo 240 mg every two weeks and Yervoy 1 mg/kg every six weeks until disease progression, unacceptable toxicity, or up to a maximum of two years.¹

Patients in the experimental cohort were administered eight intradermal injections of UV1 across the first three months of treatment. The study’s primary objective was a clinically meaningful progression-free survival benefit in patients with MPM who experienced progression on first-line standard platinum doublet chemotherapy.

The UV1 plus Yervoy and Opdivo combination was found to lower the risk of death by 27% with a median OS of 15.4 months compared to 11.1 months for Yervoy and Opdivo alone across a median observation time of 17.3 months. This achieved the protocol's predefined threshold for statistical significance.²

There was also an observed benefit in objective response rate, as determined by blinded independent central review. Investigators found that 31% of patients in the UV1 cohort experienced an objective response vs. 16% in the control cohort.²

The trial did not produce any additional safety concerns associated with UV1 treatment. Investigators will continue to monitor adverse events reported by patients across both cohorts of the NIPU study.¹

The data from the NIPU clinical trial led to the FDA granting UV1 with Orphan Drug Designation (ODD) on October 9, 2023.³ The drug was also granted ODD by the FDA in December 2021 for metastatic melanoma.⁴

References

1. Ultimovacs Receives FDA Fast Track Designation for UV1 Cancer Vaccine for the Treatment of Patients with Unresectable Mesothelioma. Ultimovacs ASA. News release. February 5, 2024. https://ultimovacs.com/investors/news/ultimovacs-receives-fda-fast-track-designation-for-uv1-cancer-vaccine-for-the-treatment-of-patients-with-unresectable-mesothelioma

2. 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. Ultimovacs ASA. News release. October 23, 2023. February 5, 2024. https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=4405256&lang=en-GB&companycode=no-ulti&v=

3. Ultimovacs Receives FDA Orphan Drug Designation for the UV1 Cancer Vaccine for Treatment of Mesothelioma. Ultimovacs ASA. News release. October 9, 2023. February 5, 2024. https://ultimovacs.com/investors/news/ultimovacs-receives-fda-orphan-drug-designation-for-the-uv1-cancer-vaccine-for-treatment-of-mesothelioma

4. Ultimovacs Granted Orphan Drug Designation by FDA for UV1 Cancer Vaccine in Metastatic Melanoma. Ultimovacs ASA. News release. December 2, 2021. February 5, 2024. https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=4002072&lang=en-GB&companycode=no-ulti&v=