Ultimovacs ASA announced encouraging overall survival (OS) data from cohort 1 in the UV1-103 Phase I clinical trial in malignant melanoma. Among the patients in cohort 1 who were alive at the 3-year follow-up, no further deaths have been reported, reaffirming an encouraging trend of durable overall survival benefit from UV1 vaccination. he UV1-103 study evaluates Ultimovacs? universal cancer vaccine, UV1, in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab, as first-line treatment in patients with advanced non-resectable or metastatic malignant melanoma. The study enrolled 30 patients in the U.S. in two cohorts that differed only in the concentration of GM-CSF used as vaccine adjuvant. Three patients in cohort 1 chose not to be followed up after 2 years. Measured in absolute numbers, the overall survival in cohort 1 after 3-year follow-up was 71% (12 out of 17 patients). Out of the 17 patients included in the 4-year follow-up, one patient could not be reached temporarily, and the status is pending. Employing a conservative approach, 11 out of 16 patients were confirmed alive after 4 years, indicating an overall survival of 69% based on absolute numbers. Overall survival from the trial based on Kaplan-Meier estimates is described below. The 4-year survival across both cohorts is expected to be announced in Second Quarter 2024. Ultimovacs has previously reported data showing a complete response rate in the UV1-103 study of 33% (complete disappearance of tumors) and an objective response rate of 57% (complete or partial disappearance of tumors). Biomarker analyses reported in October 2022 showed robust clinical responses in patients treated with the combination of UV1 and pembrolizumab, regardless of patients? PD-L1 status. The safety profile of UV1 in combination with pembrolizumab is comparable to that of pembrolizumab alone. Ultimovacs is investigating UV1 in malignant melanoma in its randomized Phase II INITIUM trial of UV1 in combination with ipilimumab and nivolumab. The trial completed enrollment of 156 patients with advanced non-resectable or metastatic malignant melanoma in July 2022. The top-line results will be disclosed after cancer progression has been verified in 70 patients, which has not yet occurred due to patients taking longer than estimated to experience cancer progression. The outcome of the study is now expected to be announced in the first half of 2024. This US-based Phase I clinical trial evaluates the Company?s lead candidate, UV1, combined with the anti-PD-1 checkpoint inhibitor, pembrolizumab, as a first-line treatment in patients with unrespectable 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 granulocyte-macrophage colony-stimulating factor (GM-CSF) used as vaccine adjuvant. The 20 patients in the first cohort received a 37.5 mcg GM-CSF adjuvant dose per UV1 vaccination. The 10 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) Out of the 9 deaths, 4 happened during the first year, 4 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. Overall survival in UV1-103 based on absolute numbers (conservative approach, only including confirmed surviving patients):1-year: Cohort 1: 85.0% (n= 17/20) I Cohort 2: 90% (n= 9/10) I Both cohorts: 86.7% (n= 26/30)2-year: Cohort 1: 80.0% (n= 16/20) I Cohort 2: 60% (n= 6/10) I Both cohorts: 73.3% (n= 22/30)3-year: Cohort 1: 70.6% (n= 12/17) I Cohort 2: 60% (n= 6/10) I Both cohorts: 66.7% (n= 18/27)4-year: Cohort 1: 68.8% (n= 11/16) I Cohort 2: N.A. I Both cohorts: N.A. The Kaplan-Meier survival curve is defined as the probability of surviving in a given length of time while considering time in many small intervals. Overall survival in UV1-103 based on Kaplan-Meier estimates:1-year: Cohort 1: 85.0% I Cohort 2: 90% I Both cohorts: 86.7%
2-year: Cohort 1: 80.0% I Cohort 2: 60% I Both cohorts: 73.3%-year: Cohort 1: 73.8% I Cohort 2: 60% I Both cohorts: 69.5%4-year: Cohort 1: 73.8% I Cohort 2: N.A. I Both cohorts: N.A. As a historical reference (not a head-to-head comparison since dosing and the patient population differ), the registration study Keynote-006 for pembrolizumab reported a 48-month overall survival rate of 45.7%. In December 2021, 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.