Clinical studies

Treatment in three Phase I studies have been completed and patients are currently followed up for survival, immune response and new anti-cancer treatment. Fifty-two (52) patients have been enrolled in these studies.

Phase I study – UV1 + anti-PD1

A new study Phase I with UV1 in combination with pembrolizumab in first line malignant melanoma patient has been approved by the FDA (IND approval) and by Ethical Committees (IRBs) at US sites. Enrollment of patients started July 2018. In this phase 1 study the safety and tolerability of treatment with the combination of pembrolizumab (PD1 inhibitor) and UV1 in 20 patients with metastatic malignant melanoma is investigated.

Registration study – UV1 + anti-PD1

Ultimovacs is currently planning for a randomized registration trial with the combination treatment of pembrolizumab and UV1 in patients with metastatic malignant melanoma. Ultimovacs intends to apply for marketing approval for UV1 in combination with anti-PD-1 based on data from the ongoing phase I study investigating the safety and tolerability of UV1 in combination with anti-PD-1 in metastatic malignant melanoma, and a planned pivotal phase II study investigating UV1 in combination with anti-PD-1 in the same indication (intended study initiation Q4 2019).

The rationale for the UV1/anti-PD-1 (Keytruda/pembrolizumab) combination in metastatic malignant melanoma is based on the following:  The current standard of care for patients with metastatic malignant melanoma without targetable genetic aberrations is PD-1 inhibitors (pembrolizumab/nivolumab). The approved use of pembrolizumab for this patient group is based on the result of the pivotal KEYNOTE-006 study where a statistically significant improvement in progression free survival (PFS) and overall survival (OS) were demonstrated with pembrolizumab when compared to ipilimumab in patients with metastatic malignant melanoma.

Despite the developments in treatment of patients with malignant melanoma with immunotherapy, the majority of the patients will not become long term survivors. Many patients do not respond, and tumor escape mechanisms is a challenge. PD-1 therapy is effective primarily in tumors with pre-existing T cells and therapy may therefore be limited by the size of the pool and specificity of pre-existent T cells. It is therefore still a need for development of new treatments options with the potential to provide extended progression free survival and overall survival in a larger proportion of malignant melanoma patients.

The studies on UV1 in combination with pembrolizumab will investigate the potential of UV1 to augment the size of the pool and the specificity of tumor specific T cells in patients with limited or insufficient numbers of T cell clones spontaneously primed by tumor antigens. UV1 can thereby provide a broader repertoire of T cells for pembrolizumab to work on. When used in combination, UV1 and pembrolizumab has the potential to entail synergetic effects and increase the clinical benefit in patients with metastatic malignant melanoma.

The objectives of the two studies on UV1 in combination with anti-PD-1 in metastatic malignant melanoma include to obtain efficacy and safety data on the combination therapy. The experimental objective of these studies is to establish a relevant biobank of patient material for characterization of the immunological response and changes in the tumor milieu promoted by UV1 induced T cells.

Proof of concept study – UV1 + anti-PD1 + anti-CTLA4

UV1 in combination with anti-PD-1 plus anti-CTLA-4 in metastatic malignant melanoma. Ultimovacs plan to sponsor a proof of concept study investigating UV1 in combination with anti-PD-1 plus anti-CTLA-4 versus anti-PD-1 plus anti-CTLA-4 in patients with metastatic malignant melanoma. The study aims to obtain safety data of the triple combination as well as signals of clinical efficacy, as well as mechanistical information on the mode of action of the vaccine induced T cells. The study is expected to give data supporting decision making regarding extension of indication for UV1.

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.