Phase I trials

Treatment with UV1 has been assessed in three Phase I studies (metastatic prostate cancer, metastatic non-small cell lung cancer and metastatic malignant melanoma) in 52 patients at the Oslo University Hospital. The observed clinical outcomes from the three completed trials served as a strong basis for the further clinical development of UV1, both with respect to safety, immune response and signals of clinical effect. In addition, Ultimovacs is the sponsor of the fully enrolled and ongoing Phase I clinical study in the U.S. evaluating the safety and tolerability of treatment with UV1 and pembrolizumab (PD-1 checkpoint inhibitor) in 30 patients with metastatic malignant melanoma.

Ongoing Phase I trials

Malignant melanoma

Ultimovacs is the sponsor of a fully enrolled and ongoing Phase I clinical study in the U.S. evaluating the safety and tolerability of treatment with UV1 and pembrolizumab (PD-1 checkpoint inhibitor) in 30 patients with metastatic malignant melanoma. 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.

TENDU – prostate cancer

Ultimovacs has started TENDU, its first Phase I trial to test the TET technology in patients with the main objective to assess the safety of the TET technology. In TENDU, the TET technology incorporates prostate-cancer-specific antigens. The first patient was treated in February 2021. Enrollment of the first cohort (three patients dosed at 40 mcg) was completed during the second quarter in 2021, and of the second cohort (three patients dosed at 400 mcg) was completed in February 2022. The Drug Safety Monitoring Board (DSMB), a group of experts set up to monitor patient safety during a clinical trial, found no safety concerns related to the first two dose cohorts. The conclusion from the DSMB enables the dose escalation study to proceed with enrollment of patients in the third and last dose cohort (960 mcg).

The TENDU trial is being conducted at Oslo University Hospital, and in total 9 patients will be enrolled. This Phase I trial will provide valuable safety and immune activation data that will support the further development of new vaccine solutions based on the TET technology.

Phase I trials 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.