Ultimovacs ASA announced the full dataset from the NIPU clinical trial (NCT04300244) presented at the ESMO Congress 2023 in Madrid. NIPU is an investigator-initiated, randomized, multi-center, open-label Phase II clinical trial for second-line treatment in patients with malignant mesothelioma (MPM). The data from the study was published initially in a late-breaking abstract at ESMO.

Further details have now been provided in an oral presentation by the Principal Investigator at the ESMO Congress. The results showed that Ultimovacs? cancer vaccine UV1, in combination with ipilimumab and nivolumab, demonstrated a statistically significant and clinically meaningful improvement in overall survival versus ipilimumab and nivolumab alone, a key secondary endpoint.

No additional safety concerns were reported from the UV1 treatment. UV1 plus ipilimumab and nivolumab improved overall survival (OS), reducing the risk of death by 27% (hazard ratio (HR)=0.73 [80% CI, 0.53-1.00], 1-sided p value = 0.0985, 2-sided p value = 0.197). The median OS was 15.4 months (95% CI, 11.1-22.6) for UV1 plus ipilimumab and nivolumab (treatment arm) versus 11.1 months (95% CI, 8.8-18.1) for ipilimumab and nivolumab alone (control arm), with a median observation time of 17.3 months.

This degree of improvement met the protocol's predefined threshold for statistical significance. The data further demonstrated a benefit in terms of objective response rate (tumor reduction by at least 30%), as determined by blinded independent central review (BICR). In the UV1 arm, 31% of the patients experienced an objective response, compared to 16% in the control arm (odds ratio 2.44 [80% CI, 1.35-4.49], 1-sided p value = 0.028).

The baseline patient characteristics were well balanced between the two treatment arms. The epithelioid subtype of MPM comprised 77.1% of the study population, in line with the frequency of this subtype among the general MPM population. Notably, the trial enrolled a relatively high fraction of patients with PD-L1 negative tumor biopsies (53.4%), a characteristic for patients typically less responsive to checkpoint inhibitors alone. The safety profile of the combination of UV1 plus ipilimumab and nivolumab observed in the trial was consistent with the safety profile of ipilimumab and nivolumab alone, confirming the good safety profile for UV1.

The patients will continue to be monitored for efficacy and safety endpoints over the next years. The NIPU study is sponsored by Oslo University Hospital with support from Bristol-Myers Squibb and Ultimovacs. The randomized, open-label, multi-center trial with 118 patients was conducted in Australia, Denmark, Norway, Spain, and Sweden.

The trial enrolled patients with malignant mesothelioma after first-line treatment with platinum-based chemotherapy. The first patient in the NIPU trial was enrolled in June 2020, and the last patient was enrolled in January 2023. The NIPU trial was designed to detect a clinically meaningful difference between the two treatment groups and includes a statistical analysis plan typical for randomized phase 2 trials where the aim is to assess efficacy without recruiting a large number of patients.

Both the study protocol and the statistical plan were approved by the regulatory authorities. It was set up with 80% statistical power and a 1-sided alpha of 0.1. This means can be 80% confident that we've accurately measured the effects of UV1. According to the trial protocol and the number of patients included, the trial results are presented with 80% confidence intervals and are considered statistically significant if the one-sided p-value is below 0.1. Ultimovacs announced topline NIPU study results in June 2023.

Based on BICR, the study did not meet the primary endpoint of PFS. Investigator assessment, a pre-defined supportive analysis of the primary endpoint performed by specialized radiologists at the study hospitals, showed a statistically significant positive PFS benefit for the patients in the UV1 arm. The HR per BICR was 1.01 (80% CI 0.75-1.36, 1-sided p value = 0.4895, 2-sided p value = 0.979), with a median PFS of 4.2 months (95% CI 2.9-9.8) for UV1 plus ipilimumab and nivolumab, and 4.7 months (95% CI 3.9-7.0) for ipilimumab and nivolumab alone.

The HR per investigator assessment was 0.60 (80% CI 0.45-0.81, 1-sided p value = 0.0125, 2-sided p value = 0.025), with a median PFS of 4.3 months (95% CI 3.0-6.8) for UV1 plus ipilimumab and nivolumab and 2.9 months (95% CI 2.4-5.5) for ipilimumab and nivolumab alone. In October 2023, Ultimovacs announced that the U.S. Food and Drug Administration (FDA) had granted Orphan Drug Designation for UV1 in the treatment of mesothelioma (based on the NIPU data from June 2023). UV1 is a therapeutic cancer vaccine that generates an immune response against the human telomerase (hTERT) enzyme.

The enzyme is essential for the ability of cancer cells to proliferate. Telomerase is present in 85-90% of all cancers, across the stages of the disease. The vaccine is manufactured as an off-the-shelf product with a long shelf life.

UV1 is easy to use and does not require sophisticated hospital infrastructure, enabling patient access to therapy also in community centers, and in rural and underserved communities. Ultimovacs is evaluating the universal cancer vaccine UV1 in a broad clinical development program across various cancer indications with different biology and disease stages, in combination with different checkpoint inhibitors. The topline data from NIPU are the first results among the five randomized trials in the UV1 Phase II clinical program.

In addition to malignant mesothelioma, Phase II studies are ongoing in patients with malignant melanoma, head and neck cancer, ovarian cancer, and non-small cell lung cancer. The topline data from the malignant melanoma and head and neck cancer trials are expected during the first and second half of 2024. UV1 is a patented, proprietary technology owned by Ultimovacs.