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.
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.
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)
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.