Clinical studies

Ultimovacs has a broad phase II development program for UV1 with more than 500 patients in four phase II trials One phase I trial is ongoing and three phase I trials have been completed were patients are currently followed up for survival, immune response and new anti-cancer treatment.

Phase II Development program

Phase II study – Malignant melanoma (INITIUM)

INITIUM is an Ultimovacs-sponsored randomized Phase II trial for first-line treatment of patients with metastatic malignant melanoma. Patients will be administered UV1 in combination with ipilimumab (CTLA-4 checkpoint inhibitor) and nivolumab (PD-1 checkpoint inhibitor). The trial will be run in the US and Europe, including Norway. In total, 154 patients will be enrolled, 77 patients will receive nivolumab and ipilimumab and the other 77 patients will receive nivolumab, ipilimumab and UV1. Planned readout of the primary endpoint of progression-free survival is H2-2022. Dr. Karl Lewis, University of Colorado Hospital, has been appointed as International Coordinating Investigator of the INITIUM trial. In total, approximately 40 sites are planned to be opened for this trial in Norway, Belgium, UK and USA.

Checkpoint inhibitor therapy (CTLA-4 and PD-1) is standard of care for advanced malignant melanoma. However, still many patients do not have long time response to the treatment and only 50% survive 5 years. Ultimovacs hopes UV1 vaccination will increase the response rate further for this patient group. If successful, the combination therapy will be a significant innovation and address a large medical need.

Malignant melanoma is a type of skin cancer that develops when melanocytes (the cells that give the skin its tan or brown color) start to grow out of control. Malignant melanoma is less common than other types of skin cancers, but more dangerous because it is much more likely to spread to other parts of the body if not diagnosed and treated at an early stage. Malignant melanoma can develop anywhere on the skin, but it is more likely to start on the trunk (chest and back) in men and on the legs in women. The neck and face are other common sites.

Phase II study – Mesothelioma (NIPU)

NIPU is a randomized, multi-center Phase II trial in which the universal cancer vaccine, UV1, will be evaluated in combination with the checkpoint inhibitors ipilimumab and nivolumab as second-line treatment in mesothelioma. Oslo University Hospital is the sponsor of the NIPU study. Bristol-Myers Squibb and Ultimovacs have entered into agreements with OUS to support the preparations and execution of the trial. A total of 118 patients will be included in the NIPU study. Half of the patients will be treated with the combination of UV1, ipilimumab (CTLA-4 checkpoint inhibitor) and nivolumab (PD-1 checkpoint inhibitor), whereas the other half will receive nivolumab and ipilimumab only.

The study is planned to be conducted at six hospitals in five countries (Norway, Sweden, Denmark, Spain and Australia). The first patient was enrolled at the Oslo University Hospital (OUS) in June 2020. The objective of the study is to achieve a clinically meaningful progression-free survival (PFS) benefit in patients with malignant pleural mesothelioma (MPM) after progression on first-line standard platinum doublet chemotherapy. The primary endpoint of the trial is progression-free survival and the PFS read-out is planned for H2-2022.

MPM is a rare malignant tumor originating from the cells lining the mesothelial surface in the lungs. MPM is the most common type of mesothelioma and is a disease with a high unmet medical need with a median overall survival of approximately one year. Most patients are treated with palliative chemotherapy. Patients with disease progression after first-line therapy have few therapeutic options. Asbestos exposure is heavily linked to the development of the disease. It may take 10 – 50 years for symptoms of mesothelioma to manifest after initial asbestos exposure. Even though the use of asbestos to a large extent is banned today, new incidences of mesothelioma will continue to be a medical challenge for decades.

Phase II study – Ovarian cancer (DOVACC)

DOVACC (Durvalumab Olaparib VACCine) is a multi-center, multinational, randomized Phase II clinical collaboration trial with the Nordic Society of Gynaecological Oncology – Clinical Trial Unit (NSGO-CTU), the European Network of Gynaecological Oncological Trial Groups (ENGOT) and AstraZeneca. The trial is sponsored by the NSGO, the leading gynaecological oncology research society in the Nordic and Baltic regions.

The trial is designed to evaluate Ultimovacs’ proprietary UV1 cancer vaccine in combination with AstraZeneca’s durvalumab, a PD-L1 checkpoint inhibitor and its PARP inhibitor, olaparib, the maintenance therapy for BRCA-mutated, advanced ovarian cancer. The trial will be conducted at more than 40 hospitals in as many as 10 European countries. The Company expects to treat the first patient around mid-year 2021. Topline data on the primary endpoint is expected in 2023.

The second-line maintenance study will enroll patients with high-grade BRCA-negative ovarian cancer after partial or complete response following the second round of chemotherapy. The study includes three arms treating a total of 184 patients. The first arm will enroll 46 patients receiving the PARP inhibitor olaparib. The 46 patients enrolled in the second arm will receive olaparib and the checkpoint inhibitor durvalumab. The third arm will include 92 patients that will receive Ultimovacs’ UV1 vaccine in combination with both AstraZeneca drugs. The primary endpoint is progression-free survival (PFS) in the treatment arm with PARP inhibitor olaparib monotherapy, versus PFS in the triple combination treatment arm. Under the terms of the collaboration, Ultimovacs will provide its UV1 vaccine and AstraZeneca will provide the PD-L1 and PARP inhibitors for the study.

Phase II studyHead and Neck cancer (FOCUS)

The FOCUS trial (First-line metastatic Or recurrent HNSCC/Checkpoint inhibitor UV1 Study) is an investigator-sponsored, randomized Phase II clinical trial that will recruit patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma. The trial will be conducted at 10 sites across Germany and led by principal investigator Prof. Mascha Binder, M.D., Medical Director and Head of the Immunological Tumor Group at University Medicine Halle, Germany, who is a renowned oncology clinician and researcher specializing in the analysis of immuno-oncology treatments and their interaction with tumor tissues.

The trial will evaluate the addition of UV1 to a standard of care treatment with PD-1 checkpoint inhibitor pembrolizumab as compared to pembrolizumab monotherapy. A total of 75 patients indicated for treatment with pembrolizumab will be enrolled in the FOCUS study, randomized 2-to-1 so that 50 patients will receive UV1 and pembrolizumab and 25 patients will receive pembrolizumab alone. The primary endpoint of the study is the progression-free survival rate at 6 months. The Company expects to treat the first patient around mid-year 2021. Top line data on the primary endpoint is expected in 2023.

Head and neck cancer is the term used to describe a number of different malignant tumors that develop in or around the throat, larynx, nose, sinuses, and mouth. Globally, head and neck cancer accounts for 650,000 new cases of cancer and 330,000 deaths annually on average. In 2018, it was the seventh most common cancer worldwide with 890,000 new cases documented and 450,000 dying from the disease. The usual age at diagnosis is between 55 and 65 years old, and the average 5-year survival following diagnosis in the developed world is 42-64%.

Ongoing Phase I study

Phase I study – Malignant melanoma

Phase I study with UV1 in combination with pembrolizumab (PD-1 inhibitor) in first line metastatic malignant melanoma patients. Safety and tolerability of treatment will be investigated with the combination in 30 patients on three sites in the USA. Enrolment of patients started in July 2018 and was completed in August 2020.

Malignant melanoma is a type of cancer that develops from the pigment-containing cells known as melanocytes. Melanomas typically occur in the skin but may also occur in the intestines, mouth or the eyes. Worldwide over 280,000 new cases of malignant melanoma were diagnosed in 2018, and it is estimated that more than 60,000 persons died from the disease.

Phase I studies in long-term follow-up

Prostate cancer

(EudraCT No. 2012-002411-26)

Prostate patients with advanced disease without lung and/or liver metastases were enrolled. These patients had started CAB treatment (GnRH-agonist combined with anti-androgen) prior to UV1 treatment.

Non-small cell lung cancer (NSCLC)

(EudraCT No. 2012-001852-20)

In the lung study stage 3b/4 NSCLC patients were enrolled, who previous had been treated with palliative radiotherapy and /or at least two courses of chemotherapy. These patients were not to be in progression, confirmed by CT, at least 4 weeks prior to UV1 treatment.

Malignant Melanoma – UV1 in combination with ipilimumab

(EudraCT No. 2013­005582­39)

The malignant melanoma patients had unresectable or metastatic disease when enrolled, and were eligible for ipilimumab. Safety and tolerability were primary endpoints in all three studies, while immune response towards any of the UV1 peptides and efficacy were secondary endpoints. Three different dose levels of UV1 were investigated in the prostate cancer and NSCLC studies (100, 300 and 700 µg). In the malignant melanoma study, 300 µg UV1 was given in combination with ipilimumab.

Data from the three studies showed that UV1 is generally well tolerated. There were no dose limiting toxicities. UV1 induced an immune response (hTERT specific T-cells) in 78% (range 67-91%) of patients across the three studies.
When combining UV1 with ipilimumab, a CTLA-4 checkpoint inhibitor, 91% of malignant melanoma patients developed an immune response. The responses appeared earlier, required fewer vaccinations, and were stronger and more long lasting compared to vaccination with UV1 alone. These data are compatible with a mechanism of action where blocking CTLA-4 checkpoints induce additional expansion of UV1 specific T cells induced by UV1 vaccination.