Malignant melanoma is the deadliest form of skin cancer. This type of cancer develops when DNA is damaged in the skin cells that produce melanin, the substance that gives skin its color. This usually occurs after prolonged exposure to ultraviolet radiation, which comes mostly from the sun. The damaged DNA causes uncontrolled cell growth, which in turn leads to tumor formation.
If detected early, melanoma is relatively easy to treat and the most common treatment is surgery. However, treating advanced malignant melanoma where surgery is not possible can be more challenging and until recently there were no reasonable treatment options. This has changed with the development of targeted immunotherapy, specifically checkpoint inhibitors (CPIs).
Ultimovacs is pushing for better treatments
Although more recently developed combination immunotherapies have the potential to extend survival for up to several years in some patients, the prognosis for metastatic melanoma remains poor. Even after the introduction of immunotherapies, between one-third and one-half of patients still do not respond to treatment, resulting in early death. There is therefore a significant need for improved treatments with an acceptable safety profile.
The Norwegian Immuno-Oncology Company Ultimovacs is working to meet this need with its universal cancer vaccine, UV1, which is being developed and tested in combination with some of the best-selling immunotherapies on the market with the aim of increasing their overall effectiveness. The company has a broad clinical development portfolio and advanced malignant melanoma is one of the indications chosen to test UV1.
New promising data in melanoma patients
One of the clinical studies being run by Ultimovacs is an ongoing open-label Phase I study testing UV1 in combination with the checkpoint inhibitor pembrolizumab in patients with malignant melanoma. This study is being conducted in the US and is led by Dr. Yousef Zakharia who is an associate professor of medicine at University of Iowa and who leads the phase I study at Holden Comprehensive Cancer Center, one of the best oncology institutes in the United States.
In late May, Ultimovacs announced an update from a 21-month follow-up of the first group of patients in this study. The results show an objective response rate (ORR) of 60 percent (which indicates the proportion of patients experiencing tumor reduction or tumor disappearance), with all patients having been observed for at least 18 months and with a median observation time of 21 months. For more information on the results, read here.
»Certainly, this early data seems promising and encouraging, I am anxious to see the results of larger clinical trials utilizing this new vaccine. Given the mechanism of action, I anticipate that this could be utilized in melanoma or other malignancies« — Yousef Zakharia, MD, Associate Professor of Medicine at the University of Iowa
Overall, the results, although early and from a small group of patients, show a significant improvement over what is currently seen as conventional treatment options. In particular, they point to a significant improvement over pembrolizumab as a stand-alone treatment, lending weight to the hypothesis that UV1 enhances the efficacy of other immunotherapies.
Lead investigators discuss data
Ultimovacs presented this data at the virtual American Society of Clinical Oncology (ASCO) Annual Meeting 2021 held this past weekend, the largest international oncology conference where more than 30 doctors normally attend from all parts of the world.
BioStock contacted Dr. Zakharia to get his perspective on the exciting results.
Dr Zakharia, thank you for joining us, what is your experience with clinical trials and what led you to take on this particular study?
- Thank you for reaching out, I tell my patients that being at an NCI Designated Comprehensive Academic Cancer Center, we prefer to treat our patients on clinical trials to increase their treatment options and that is how we advance the science. What lead us to participate in this clinical trial is the innovative combination, the mechanism of action of this drug and encouraging pre-clinical data.
What does it mean to you to be able to work with these patients and insert them into this trial?
- It is an unparalleled feeling of excitement to see my patient's disease responding to a new innovative treatment on a clinical trial and yet tolerating the combination well.
Could you tell us, in brief, the overall scope of this phase I trial with UV1?
– This is an open label phase 1 study evaluating the safety and tolerability of UV-1 and GM-CSF in combination with standard of care pembrolizumab as a first-line treatment in patients with metastatic melanoma, the study has 2 arms with 2 different doses of GM-CSF, the results we presented at ASCO 2021 are for 20 patients who received UV1 with adjuvant GM-CSF 37.5 µg and pembrolizumab. The primary endpoint of the study is safety and secondary endpoint of clinical response defined as overall response rate (ORR), progression free survival (PFS) and overall survival (OS).
The team at Ultimovacs are quite excited about the results from this study so far. What is so encouraging about this data?
- The combination was safe and well-tolerated, and the general side effects were similar to what we would expect with single agent pembrolizumab, other than injection site reaction related to UV 1 vaccine and managed conservatively. The efficacy data is encouraging with ORR of 60 per cent, CR of 30 per cent and median PFS of 18.9. Frankly speaking, this is still early results on small cohort of patients, however the efficacy signal of the combination is encouraging enough and worth further investigation in larger clinical trials which are ongoing.
Has UV1 impressed you as an immunotherapy and, from your perspective, how broad is its therapeutic potential?
- Certainly, this early data seems promising and encouraging, I am anxious to see the results of larger clinical trials utilizing this new vaccine. Given the mechanism of action, I anticipate that this could be utilized in melanoma or other malignancies.
Finally, where does this study go from here?
– UV1 is currently being evaluated in a phase II study in combination with ipilimumab and nivolumab in advanced melanoma.
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