Mesothelioma is a rare but aggressive form of cancer with limited treatment options. Norwegian biotech company Ultimovacs is addressing the need for new therapies with its universal cancer vaccine UV1. BioStock reached out to Ultimovacs Director Medical Affairs, Espen Basmo Ellingsen, to learn more about the overall burden of the disease, as well as the Phase II NIPU trial evaluating UV1 in combination with standard of care.
Asbestos is a naturally occurring mineral known for its heat-resistant and anti-corrosion properties. During the 1800th century and much of the 1900th century, asbestos was often used as an insulating material in the construction of buildings, as well as for other industrial applications.
The toxic, carcinogenic properties of asbestos were discovered and studied in the early 1900s when scientists noticed a large number of early deaths and lung problems in asbestos mining towns. However, it was not until the latter part of the century that many governments, including those in the US and the EU, imposed severe restrictions and even outright bans on the use of asbestos.
Despite these bans, the average latency period for the development of health problems related to asbestos exposure is approximately 40 years. This places former and current workers who have come into direct contact with asbestos at an increased risk of health complications. Those in the construction industry are most affected, but also firefighters in particular.
Mesothelioma – a deadly disease
One of the leading causes of death from asbestos exposure is mesothelioma, an aggressive form of cancer that develops in the lining of the internal organs. The most common type of mesothelioma is malignant pleural mesothelioma (MPM), which affects the thin layer of tissue that surrounds the lungs and the inside of the chest. The disease often leads to a life expectancy of less than a year after diagnosis, and the 5-year survival rate is 12 percent.
MPM is so aggressive that the disease is usually diagnosed in the late stages, making treatment extremely challenging. At that point, surgery is possible, but is usually accompanied by chemotherapy. As of 2020 in the US and 2021 in Europe, immune checkpoint inhibitors such as nivolumab and ipilimumab also become first-line treatment.
However, although these treatments may initially reduce the cancer, recurrence is very likely. When the disease relapses, it becomes more resistant to treatment and escapes the immune system's defenses, further reducing the chances of survival. Unfortunately, there is currently no standard treatment for relapse in malignant mesothelioma, which means there is a significant medical gap to fill.
Ultimovac cancer vaccine
One biotech company that is striving to fill this gap is UltimovacsThe Nordic biotechnology company is developing UV1, a universal cancer vaccine that aims to strengthen the patient's immune system enough to slow the cancer. The company has five ongoing Phase II clinical trials evaluating UV1 in various cancer indications – the NIPU trial is the one focusing on mesothelioma.
Read more about Ultimovacs and the company's pipeline here.
The study evaluates UV1 as a second-line treatment in combination with both checkpoint inhibitors nivolumab and ipilimumab. Research conducted to date with UV1 suggests that the therapeutic vaccine can work in conjunction with immune checkpoint inhibitors to unleash the full power of the immune system to attack the cancer in the event of a relapse.
A first readout from the study is expected in the coming weeks. The results, if positive, will constitute proof-of-concept for UV1 in this indication, and thus a major step forward in the development of the vaccine.
A conversation with Ultimovac's DMA
BioStock contacted Ultimovac's Director Medical Affairs Espen Basmo Ellingsen to discuss the challenges related to mesothelioma and how the disease should be treated, as well as expectations for the NIPU study.
Espen, why is mesothelioma such a difficult disease to treat?
Mesothelioma is a rare and aggressive disease characterized by irregular growth of the mesothelial cells, which form the protective lining of internal organs. The early symptoms of mesothelioma can be similar to those of less severe respiratory conditions. Mesothelioma, therefore, often goes undiagnosed in its early stages, and by the time a definitive diagnosis occurs, the cancer is typically more advanced, resulting in fewer therapeutic options and an established tumor biology that is harder to treat. Mesothelioma has been shown to harbor genetic and molecular characteristics that make the cancer cells less susceptible to conventional treatments. For immunotherapies specifically, the tumors may hold certain immunosuppressive features that counteract the spontaneous anti-tumor immune responses.
What is the difference between first-line and second-line treatment in cancer therapy?
Treatment lines refer to the order treatments are given as a tumor progresses or recurs. For advanced cancers, first-line treatment refers to the initial treatment alternative a patient receives after diagnosis, whereas second-line treatment refers to the treatment alternative the patient receives after the disease progresses on first-line treatment. Each successive treatment line is initiated when the previous treatment is no longer effective or the disease has shown resistance to it. The goal of the different treatment lines is to provide additional therapeutic options to control the disease and extend survival. However, generally, the later the treatment line, the less response to therapy is expected.
Why isn't UV1 being evaluated as a first-line treatment?
The NIPU trial evaluates UV1 in combination with nivolumab and ipilimumab as second-line therapy. At the time the trial was initiated, there were no approved immunotherapies for malignant pleural mesothelioma. It is common to evaluate experimental treatments in later treatment lines, when standard treatment options have been exhausted. However, with the recent approval of the checkpoint inhibitors nivolumab and ipilimumab as first-line therapy, positive results from the NIPU trial may facilitate further development of UV1 in the first-line setting.
Why is NIPU looking at UV1 in a triple combination with both nivolumab and ipilimumab, and not in combination with chemotherapy or even on its own?
Nivolumab and ipiliumab represent drugs that are classified as immune checkpoint inhibitors. Physiologically, the immunological checkpoints are the body's way of containing T cell responses within a desired range, maintaining a balance between attacking harmful invaders and avoiding unnecessary damage to healthy cells. During the development of cancer, however, tumors exploit these checkpoint molecules to evade an attack from the patient's T cells. When a patient receives a checkpoint inhibitor, naturally occurring T cells targeting the tumors can be released from these constraints, leading to cancer cell killing. Although many patients experience durable responses to checkpoint inhibition, unfortunately, most patients progress due to an insufficient natural immunity against the tumors.
Therapeutic vaccination with UV1 induces T cell responses that aim to strengthen the overall anti-tumor immune response. The combination of UV1 and the checkpoint inhibitors is based on a scientific rationale that releasing the immune cells from these immune checkpoints will result in stronger immune responses after vaccination, and that these immune cells will more effectively kill cancer cells. Although both being checkpoint inhibitors, the two drugs differ in the immune checkpoint molecule they block. Ipilimumab blocks CTLA-4, whereas nivolumab blocks PD-1. Blocking CTLA-4 is expected to strengthen the immune response after vaccination, whereas blocking PD-1 is expected to reduce the tumor's ability to resist the induced immune response. With the characteristic features of mesothelioma, we believe the triple combination may be necessary to overcome the immunosuppressive tumor microenvironment and provide tangible cancer cell killing.
When can we expect top-line results from NIPU?
Topline results from the NIPU trial are expected to occur this month of June, so rather soon.
If the study brings positive results, what will it mean for UV1 and the future development, especially considering that mesothelioma is considered a rare disease?
If the NIPU trial reads positive:
it will prove the overall concept of UV1 as a telomerase targeted vaccine works when added to CPIs, and increases the probability of success in the other indications
further development plans will be discussed with the regulatory authorities to ensure the most effective and speedy way forward. This also includes filing for breakthrough/fast track designation, and orphan drug designation
it will definitely trigger further support for bringing UV1 to mesothelioma patients, a population with a true unmet medical need.
The imminent read-out of the NIPU trial represents the first-ever randomized data package on the UV1 vaccine. Following closely are the read-outs of the randomized INITIUM trial in melanoma (H2 2023) and the randomized FOCUS trial in head and neck cancer (H1 2024). The DOVACC and LUNGVACC trials are expected to complete later in 2024 and 2025, respectively. The outcomes of all these trials will guide the broader development of UV1.