September 9, 2024: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-stage biotechnology company developing novel immunotherapies against cancer, announces the presentation of updated data analysis from the UV1 Phase II NIPU trial (NCT04300244), at the 2024 ESMO Congress. The NIPU trial evaluated the addition of UV1 telomerase vaccine to immunotherapy with ipilimumab and nivolumab compared with ipilimumab and nivolumab alone, as a second-line treatment for patients with inoperable malignant pleural mesothelioma. As presented at ESMO 2023, the trial did not meet the primary endpoint of improved progression-free survival (PFS) by blinded, independent central review (BICR), however the data showed a meaningful benefit on the key secondary endpoints including a doubling of objective response rate (ORR) and a 27% reduction in risk of death. The ESMO 2024 poster presentation highlights an increased clinical benefit observed for the epithelioid subgroup, demonstrating an improvement in median PFS of 5.5 months for UV1 in combination with ipilimumab and nivolumab, versus a median PFS of 2.9 months for immunotherapy alone. The epithelioid subtype represents approximately 70% of all patients with mesothelioma. In addition, the ESMO 2024 data presentation demonstrates a positive difference in overall survival (OS) for UV1 treatment at the latest patient follow-up, although the degree of benefit is less than previously reported.
The full results will be presented in a poster at the congress, held in Barcelona, Spain from September 13-17, 2024. The abstract is available on the Ultimovacs website (under the section 'Presentations and publications') and the poster will be available on the Ultimovacs website after the presentation on Saturday, September 14.
Title: Updated survival and vaccine response from the NIPU trial; A randomised, phase II study evaluating nivolumab and ipilimumab with or without UV1 vaccination in patients with pleural mesothelioma
Presentation Number: 1917P
Speaker: Vilde D. Haakensen, MD, PhD, Project Group Leader at the Oslo University Hospital
Date: Saturday, September 14, 2024
NIPU is an investigator-initiated, randomized, open-label, multi-center Phase II trial sponsored by Oslo University Hospital with support from Bristol-Myers Squibb and Ultimovacs. Six university hospitals in Australia, Denmark, Norway, Spain, and Sweden participated in the trial. A total of 118 patients were randomized between June 2020 and January 2023.
“Zooming in on the different subgroup analyses, we see persistent survival signs especially in the epithelioid mesothelioma patient subgroup, supporting a rationale for further investigation of UV1 in this indication, which continues to represent a high unmet medical need,” said Jens Bjørheim, Chief Medical Officer at Ultimovacs. “At Ultimovacs, our goal is to provide new treatment options for patients that do not benefit from the current standard of care and we will discuss these data and potential next steps with key stakeholders and the medical community.”
In March 2024, Ultimovacs announced the publication of the Phase II NIPU trial results in the European Journal of Cancer. Analyses of secondary endpoints, objective response rate (ORR) by BICR and overall survival (OS), showed a benefit of adding the UV1 vaccine to ipilimumab and nivolumab. The safety profile of the combination of UV1 plus ipilimumab and nivolumab observed in the trial was consistent with that of ipilimumab and nivolumab alone, confirming the good safety profile for the UV1 vaccine.
NIPU (Nivolumab and Ipilimumab Plus/minus UV1 vaccination) is a randomized, multi-center phase II trial in which Ultimovacs’ universal cancer vaccine, UV1, is evaluated in combination with Bristol-Myers Squibb’s checkpoint inhibitors, nivolumab and ipilimumab, as second-line treatment of malignant mesothelioma. The trial sponsor is Oslo University Hospital, supported in the preparation and execution of the trial by Ultimovacs and Bristol-Myers Squibb.
The 118 patients were randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity or for a maximum of 2 years. Patients randomized to the experimental arm received 8 intradermal injections of UV1 vaccine during the first three months of treatment. The objective of the study is to achieve a clinically meaningful benefit in patients with malignant mesothelioma (MPM) after progression on first-line standard platinum doublet chemotherapy. Subsequent events emerging in patients in both arms of the NIPU study will continue to be monitored beyond read-out of the primary endpoint. The ipilimumab and nivolumab combination has recently been approved as first-line treatment for patients with malignant pleural mesothelioma in Europe and the U.S.
The trial was sized to detect a target PFS HR of 0.6, with 80% power and a 1-sided alpha of 0.1. Overall survival was calculated using the same method as for PFS.
UV1 is a universal cancer vaccine designed to induce a specific T cell response against telomerase. UV1 consists of long, synthetic peptides, representing a sequence in the reverse transcriptase subunit of telomerase (hTERT), shown to induce CD4+ T cells. These CD4+ T cells have the potential to provide inflammatory signals and T cell support that are believed to be critical for triggering a strong anti-tumor immune response. Following intradermal injection, antigen presenting cells (APCs) in the skin are exposed to the vaccine peptides. These APCs will process the peptides, and present vaccine epitopes on Human Leukocyte Antigen (HLA) molecules to naïve T cells in the lymph nodes. Activated vaccine-specific T cells will then enter the circulation and search for cells displaying their cognate antigen in the context of HLA molecules.
The UV1 peptides contain several epitopes, shown to be non-restrictive in terms of (HLA) alleles for presentation. It is therefore not required to perform HLA pre-screening of patients, which potentially enables broad population utilization of the vaccine. UV1 is administered over three months as eight intradermal injections together with the immune-modulator, GM-CSF.
Ultimovacs is a clinical-stage biotechnology company developing novel immunotherapies against cancer. The product candidate UV1 is an off-the-shelf therapeutic cancer vaccine designed to enhance the benefits of immunotherapy and improve cancer treatment efficacy for patients. UV1 triggers an immune response against the shared cancer antigen telomerase, a target present in 85-90% of all cancer indications across disease stages.
Ultimovacs is investigating the safety and efficacy of UV1 in a wide-ranging clinical development program including various cancer indications and different immunotherapy combinations. The ongoing Phase II program comprises five randomized clinical trials in melanoma, mesothelioma, head and neck cancer, ovarian cancer, and non-small cell lung cancer. More than 750 patients in the U.S., Europe, and Australia are being enrolled in all Phase I and Phase II trials in the current program.
Furthermore, Ultimovacs is developing a novel conjugation technology, initially formed to support the expansion of our vaccine pipeline. With the objective of driving value and future pipeline growth, this flexible conjugation technology has the potential to be broadly applicable to a variety of therapeutic modalities, such as innovative drug conjugates with favorable pharmacological properties, and in multiple disease areas.
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