FDA Grants Fast Track Status to UVI Plus Checkpoint Inhibition for Melanoma Subgroup

The FDA has granted a fast track designation to UV1, a universal cancer vaccine, in combination with either pembrolizumab (Keytruda) or ipilimumab (Yervoy) for the treatment of unresectable or metastatic melanoma, according to a press release by Ultimovacs.¹

The designation is based on 2 separate clinical trials. The first, a phase 1 trial, looked at UV1 in combination with pembrolizumab in patients with unresectable or metastatic melanoma (NCT03538314). The second, a phase 1/2 study, compared UV1 in combination with ipilimumab (NCT02275416).¹

The first study had an actual enrollment of 30 participants and an estimated completion data of October 2022. The primary end point of the study is the number of patients with treatment-related adverse events up to week 29. Secondary end points include tumor response up to week 52 as accessed by RECIST and iRECIST and overall survival (OS). During the study, all patients received UV1 and pembrolizumab for 14 weeks.

In the first cohort of 20 patients, the 2-year OS was 80%, with a median progression-free survival (PFS) of 18.9 months. Notably, the median PFS in this study was longer compared with historic data of pembrolizumab administered with ipilimumab in patients with advanced melanoma in the phase 3 KEYNOTE-006 (NCT01866319). The 12-month OS was 85%, and at 24 months, the OS rate was 58% and the median PFS range from 5.5 months to 11.6 months. In that KEYNOT-006 study, the 24-month OS was 58% and a median PFS of 5.5-11.6 months.²

The second study had an actual enrollment of 12 participants and an estimated study completion date of February 2025. The primary end point of the study was safety and tolerability. Secondary end points include immunological response, treatment response, and health related quality of life³.

During the study, all patients received UV1 in combination with ipilimumab. Ipilimumab was given every third week for a total of 4 doses, with doses of the vaccine in between. After the third dose, patients received ipilimumab every 4 weeks for up to 28 weeks, and then again at week 36 and 48.³

The combination was found to be safe, with an objective response rate of 33% and a 5-year OS of 50%. Of the 12 patients, 3 achieved a partial response and 1 achieved a complete response. The 3-year OS was 67% Adverse events included injection site reaction and diarrhea.⁴

“We are delighted UV1 has received the Fast Track designation and look forward to working more closely with the FDA to bring UV1 to melanoma patients as soon as possible,” said Carlos de Sousa, chief executive officer of Ultimovacs, in a press release. “The FDA’s decision recognizes the potential synergy of UV1 and checkpoint inhibitors and will greatly encourage physicians and patients involved in our phase 2 clinical trial INITIUM. We remain committed to progressing UV1 in our four ongoing phase 2 clinical studies and assessing development of UV1 with pembrolizumab in advanced melanoma.”

_REFERENCE:

_{1.Ultimovacs receives dual FDA fast track designation for UV1 in advanced malignant melanoma. News release. Ultimovacs. October 21, 2021. Accessed October 21, 2021. https://bit.ly/2XyQvjf} 

_{2.UV1 vaccine with pembrolizumab for patients with unresectable or metastatic melanoma. ClinicalTrials.gov. Accessed October 14, 2021. https://bit.ly/3AEOhMM}

_{3.Safety of UV1 vaccination in combination with ipilimumab in patients with unresectable or metastatic malignant melanoma. ClinicalTrials.gov. Accessed October 21, 2021. https://bit.ly/3C3c3U7}

_{4. A phase I/IIa clinical trial investigating the therapeutic cancer vaccine UV1 in combination with ipilimumab in patients with malignant melanoma: Four-year survival update. Jour Clin Oncol. 2020;38(5):62 doiI: 10.1200/JCO.2020.38.5_suppl.62}