Ultimovacs ASA announced the publication of clinical and biomarker analyses of the UV1-103 Phase I trial in Clinical Cancer Research, a renowned peer-reviewed journal of the American Association for Cancer Research. The Clinical Cancer Research article further expands upon the clinical data presented by Dr. Yousef Zakharia at the 19th International Congress of the Society for Melanoma Research (SMR) in October 2022. The UV1-103 study evaluates the Company's universal cancer vaccine, UV1, in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab, as first-line treatment in 30 patients with advanced non-resectable or metastatic malignant melanoma.

Pembrolizumab has transformed the melanoma treatment landscape and is a standard of care in this population. Despite this, a large proportion of the patient population remains underserved due to suboptimal responses to monotherapy checkpoint inhibitors, underscoring the need for more effective treatment options. The article in Clinical Cancer Research outlines results showing that UV1 in combination with pembrolizumab has a good safety profile and encouraging signs of efficacy, in particular, extended overall survival and complete responses in 33% of the patients.

Biomarker data demonstrated equally strong responses to the combination in PD-L1 negative tumors, which are typically less amenable to monotherapy checkpoint inhibition. A drastic decrease in telomerase reverse transcriptase (TERT) was observed in responding tumors, indicating eradication of tumor cells expressing the antigen that UV1 is targeting. This US-based Phase I clinical trial is evaluating the Company’s lead candidate, UV1, in combination with the anti-PD-1 checkpoint inhibitor, pembrolizumab, as a first-line treatment in patients with unresectable metastatic malignant melanoma.

The trial evaluates safety, tolerability, and initial signs of clinical response. Thirty patients in the U.S. were treated in the study in two cohorts that differed only in the concentration of GM-CSF used as a vaccine adjuvant. The 20 patients in the first cohort received a 37.5 mcg GM-CSF adjuvant dose per UV1 vaccination.

The ten patients in the second cohort received the standard 75 mcg GM-CSF adjuvant dose per UV1 vaccination. The study has completed the enrollment of 30 patients, as announced on August 18, 2020. All included patients received the drugs as first-line treatment for advanced and metastatic malignant melanoma.

Compiled clinical results for the 30 patients enrolled are: Objective response rate (ORR): 57%. Complete response rate (CR): 33%; Median Progression Free Survival (mPFS): 18.9 months (as measured by iRECIST); Overall survival (OS) after 12 months: 87% (26/30). OS after 24 months: 73% (22/30).

OS after 36 months: 67% (18/27). Out of the nine deaths, four happened during the first year, four during the second year, and one during the third year across both cohorts. Patients will continue to be followed up for long-term survival.

Three patients in cohort 1 chose not to be followed up further after 24 months. The trial had previously reached its primary endpoint of safety and tolerability, and no unexpected safety issues related to UV1 have been observed in this trial. The U.S. Food and Drug Administration (FDA) granted a dual Fast Track designation for UV1 in combination with checkpoint inhibitors in the treatment of unresectable or metastatic melanoma – either as add-on therapy to pembrolizumab or as add-on therapy to ipilimumab.

Ultimovacs is currently evaluating UV1 as an add-on therapy to ipilimumab and nivolumab as first-line treatment of patients with unresectable or metastatic melanoma in the phase II study INITIUM.