FDA Grants Fast Track Status to Cancer Vaccine UV1 for Advanced Malignant Melanoma

FDA

The FDA has granted a fast track designation to the universal cancer vaccine UV1 for use in combination with checkpoint inhibitors in patients with unresectable or metastatic melanoma, either as an add-on therapy to pembrolizumab (Keytruda) or to ipilimumab (Yervoy).¹

The designation is based on findings from 2 phase 1 trials of UV1, where it was combined with either pembrolizumab or ipilimumab.

When the vaccine was paired with the PD-1 inhibitor in the frontline treatment of patients with advanced melanoma, it was found to be safe and to elicit early efficacy. The combination resulted in an objective response rate (ORR) of 57%, with a complete response rate of 30%. At 24 months of follow-up, 80% of patients were alive. In a second cohort of patients, similar levels of tumor elimination were reported, with 90% of patients alive after 1 year.

When combined with ipilimumab, the agent was also found to be safe and to demonstrate signals of prolonged efficacy in patients with advanced melanoma. Specifically, the combination regimen elicited an ORR of 33% in these patients. Moreover, the 5-year overall survival rate was 50%.

“We are delighted UV1 has received a fast track designation and look forward to working more closely with the FDA to bring UV1 to [patients with] melanoma as soon as possible,” Carlos de Sousa, chief executive officer of Ultimovacs, stated 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 4 ongoing phase 2 clinical studies and assessing development of UV1 with pembrolizumab in advanced melanoma.”

The UV1 vaccine is comprised of 3 long peptides covering the active site of the tumor-associated antigen telomerase. Through vaccination, patients can elicit telomerase-specific T cells with the potential of providing the necessary inflammatory tumor microenvironment for optimal immune-mediated tumor control.

In three phase 1 trials, the vaccine has been found to elicit immune responses in human leukocyte antigen–unselected patients with several tumor types, including malignant melanoma, non–small cell lung cancer, and prostate cancer.²

It has been suggested that the efficacy of checkpoint inhibitors depends on spontaneous antitumor immune responses. The vaccine works to boost the efficacy of these agents by providing the necessary antitumor responses. It is hypothesized that the checkpoint inhibitors can reciprocally provide amplified expansion and effector capacity of vaccine-induced T cells by blocking both CTLA-4 and PD-1.

In the ongoing phase 2 INITIUM trial (NCT04382664), investigators will compare the safety and efficacy of nivolumab (Opdivo) and ipilimumab with or without UV1 vaccination in the frontline treatment of patients with metastatic malignant melanoma.³

The open-label, multicenter, global phase 3 INITIUM trial is enrolling patients who are at least 18 years of age with a histologically confirmed diagnosis of unresectable stage IIIB, D, or unresectable stage IV malignant melanoma. To be eligible for enrollment, patients needed to be eligible to receive combination treatment with nivolumab and ipilimumab, to have an ECOG performance status of 0 or 1, and acceptable organ function.

Patients cannot have known brain metastases or leptomeningeal disease, a diagnosis of uveal or ocular melanoma, or a known history or any evidence of active, noninfectious pneumonitis. Other exclusion criteria include a history of congestive heart failure, active infection requiring systemic treatment, immunodeficiency, and prior systemic treatment for unresectable stage IIIB, D, or unresectable stage IV malignant melanoma, among others.

A total of 154 patients are being randomized 1:1 to receive 4 cycles of nivolumab at a dose of 1 mg/kg every 3 weeks plus 4 cycles of ipilimumab at 3 mg/kg every 3 weeks plus 8 injections of UV1 at 300 μg and 75 μg of granulocyte-macrophage colony-stimulating factor (GM-CSF) during the first 13 weeks, or 4 cycles of nivolumab at 1 mg/kg every 3 weeks plus 4 cycles of ipilimumab at 3 mg/kg every 3 weeks.

Patients in the investigative arm will receive 3 vaccinations with UV1 in week 1, 1 in week 2, and then 4 vaccinations in the subsequent 11 weeks, translating to a total of 8 vaccinations. Participants will continue to receive nivolumab maintenance treatment at 480 mg every 4 weeks, per the label.

The primary end point of the trial is progression-free survival per RECIST v1.1 criteria.

In June 2020, the first patient in the trial was dosed at the Oslo University Hospital.⁴

The vaccine is also being evaluated in combination with checkpoint inhibitors in 4 phase 2 trials that are being performed in patients with unresectable or metastatic melanoma, ovarian cancer, head and neck squamous cell carcinoma, and malignant pleural mesothelioma.

References

1. Ultimovacs receives dual FDA fast track designation for UV1 in advanced malignant melanoma. News release. Ultimovacs ASA. October 21, 2021. Accessed October 25, 2021. https://bit.ly/3EjPcV9
2. O’Day S, Bechter O, Lorigan P, et al. Abstract CT231: nivolumab and ipilimumab +/- UV1 vaccine as 1st line treatment in patients with malignant melanoma (INITIUM-trial). Cancer Res. 2021;81(13). doi:10.1158/1538-7445.AM2021-CT231
3. UV1 vaccination plus nivolumab and ipilimumab in the treatment of melanoma. ClinicalTrials.gov. Updated October 18, 2021. Accessed October 25, 2021. https://clinicaltrials.gov/ct2/show/NCT04382664
4. Ultimovacs ASA announces first patient dosed in the phase II INITIUM trial in metastatic malignant melanoma. News release. Ultimovacs ASA. June 15, 2020. Accessed October 25, 2021. https://bit.ly/3GetG5M