FDA Fast Tracks UV1, Ipilimumab, and Nivolumab in Malignant Mesothelioma

• The combination is being evaluated in the phase 2 NIPU trial (NCT04300244), which has shown encouraging results among patients with unresectable malignant pleural mesothelioma.

• Patients treated with UV1, ipilimumab (Yervoy), and nivolumab (Opdivo) had a 27% reduction in death risk and higher objective response rate (ORR) compared with the control group.

• With a fast track designation, experts will facilitate the development and expedite the review of UV1 for the treatment of patients with unresectable malignant pleural mesothelioma with the goal of bringing the agent to patients earlier.

The FDA has granted a fast track designation to the combination of UV1 with ipilimumab and nivolumab for the treatment of patients with unresectable malignant pleural mesothelioma.¹

This regulatory decision is supported by findings from the phase 2 NIPU trial which is evaluating UV1 in patients with unresectable malignant pleural mesothelioma.² Results from the study were presented at the ESMO Congress 2023 and showed there to be a clinically meaningful improvement in overall survival, reducing the risk of death by 27% (HR, 0.73; 80% CI, 0.53-1.00) among the patients treated with UV1 at 15.4 months (95% CI, 11.1-22.6) compared with ipilimumab and nivolumab alone at 11.1 months (95% CI, 8.8-18.1). The median observation time was 17.3 months.

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A benefit was also observed regarding ORR in the UV1 arm as 31% of the patients experienced an objective response vs 16% in the control arm (odds ratio, 2.44; 80% CI, 1.35-4.49). The safety profile of the combination was consistent with findings observed with ipilimumab and nivolumab alone, and there were no added toxicities reported.

“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. 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, chief executive officer of Ultimovacs, in a press release.¹

UV1 is a therapeutic cancer vaccine that generates an immune response against human telomerase, an enzyme that is necessary for the ability of cancer cells to proliferate. UV1 is an off-the-shelf vaccine with a long shelf life that is easy to use. The product does not require sophisticated hospital infrastructure, making it available to patients in community centers, rural, and underserved communities.

Previously, the FDA granted UV1 an orphan drug designation (ODD) for the treatment of mesothelioma in October 2023, an ODD for the treatment of stage IIB-stage IV melanoma in December 2021, and a fast track designation for UV1 as an add-on therapy to ipilimumab or pembrolizumab (Keytruda) for the treatment of unresectable or metastatic melanoma in October 2021.

The NIPU study is a randomized, open-label, multicenter trial evaluating the combination of UV1 with checkpoint inhibitors nivolumab and ipilimumab among 118 patients in Australia, Denmark, Norway, Spain, and Sweden. Patients with malignant mesothelioma after first-line treatment with platinum-based chemotherapy are included in the trial if they have histologically and/or cytologically confirmed malignant pleural mesothelioma, unresectable disease, measurable disease, an available unstained archived tumor tissue sample in sufficient quantity to allow for analyses, an ECOG performance status of 0–1, adequate organ function, have been previously treated with at least 1 line of platinum-pemetrexed, and are willing to provide archived tumor tissue and blood samples for research.³

The primary end point of the trial is progression-free survival per RECIST as determined by blinded independent central review assessed by radiological assessments with secondary end points of response evaluation, evaluation of patient reported outcomes, and safety and tolerability, including evaluating adverse events and the discontinuation rate of patients.

“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,” added de Sousa in the press release.¹

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 5, 2024. http://tinyurl.com/33vj8wf3

2. Ultimovacs Announces NIPU results presented at ESMO 2023: significant and clinically meaningful improvement in overall survival for patients receiving UV1 cancer vaccine in phase II NIPU trial in malignant mesothelioma. News release. Ultimovacs ASA. October 17, 2023. Accessed February 5, 2024. http://tinyurl.com/yutthma5

3. Nivolumab and ipilimumab +/​- UV1 vaccination as second line treatment in patients with malignant mesothelioma (NIPU). ClinicalTrials.gov. Updated January 25, 2023. Accessed February 5, 2024. https://clinicaltrials.gov/study/NCT04300244?tab=table