Cancer Vaccine UV1 Plus Keytruda Shows Safety, Early Efficacy in Advanced Melanoma Trial

Cancer Vaccine UV1 Plus Keytruda Shows Safety, Early Efficacy in Advanced Melanoma Trial

Adding UV1, Ultimovacs’ experimental cancer vaccine, to Keytruda (pembrolizumab) is safe and shows initial signs of effectiveness in adults with previously untreated metastatic melanoma, according to top-line data from a Phase 1 clinical trial.

“The safety profile observed to date in this first cohort [group of patients] of the [UV1-Keytruda] combination study is consistent with the promising safety profiles seen in our earlier Phase 1 trials,” Jens Bjørheim, Ultimovacs’ chief medical officer, said in a press release.

“We are encouraged by the results and look forward to additional data readouts over the next years that will demonstrate if the initial signs of efficacy in this cohort persist and mature into long-term added clinical benefit for the patients,” he added.

The UV1 vaccine works by promoting immune responses against the human telomerase reverse transcriptase (hTERT), an enzyme normally inactive in healthy cells and active in 85%–90% of all cancer cell types.

hTERT restores and maintains the length of telomeres, the protective caps at the ends of chromosomes that preserve the genetic information inside a cell.

Typically, telomeres become shorter each time a cell divides, limiting their lifespan. hTERT is therefore essential for cancer cells’ ability to live longer, and keep dividing and growing.

UV1 contains three peptides, or small parts, of hTERT, which were previously shown to promote strong T-cell responses and long-term survival benefits across different cancer types. T-cells are a type of immune cell involved in the fight against cancer.

The universal cancer vaccine is administered through repeat intradermal injections together with GM-CSF, which stimulates immune responses against cancer. An intradermal injection is given to the dermis, a skin layer that contains a large number of immune cells.

Ultimovacs aims to promote a strong immune response against the tumor while simultaneously suppressing its ability to reduce such response by combining UV1 with immune checkpoint inhibitors, such as Keytruda, which work by preventing immune evasion mechanisms often used by cancer cells.

“For the further development of our vaccine, it is important to demonstrate that UV1 can be combined with different classes of immunotherapies without compromising on safety,” Bjørheim said.

Keytruda, developed by Merck (known as MSD outside North America), blocks the interaction between the PD-1 receptor in T-cells and its ligand PD-L1 in cancer cells, boosting anti-cancer responses and promoting cancer cell death.

Currently a standard-of-care for melanoma, Keytruda was approved as a first-line treatment based on positive data from the KEYNOTE-006 Phase 3 trial (NCT01866319).

The Phase 1 clinical trial (NCT03538314), which completed enrollment in August, is evaluating the safety, tolerability, and preliminary effectiveness of adding UV1 to first-line treatment with Keytruda in 30 adults with metastatic melanoma.

Its main goal is to assess the combination’s safety, while secondary goals include tumor response and overall survival.

The first 20 patients (first group) received 37.5 micrograms of GM-CSF per UV1 vaccination (300 micrograms). Positive preliminary data allowed the testing of a higher dose of GM-CSF (75 micrograms) per vaccination in 10 additional patients (second group).

At the data cut-off date of Sept. 30, every patient in the first group had at least 12 months of post-treatment follow-up. At one-year, 85% of them were alive, and more than half did not show signs of disease progression.

To date, UV1 has been well tolerated, with a safety profile consistent with that previously reported for each therapy and with no unexpected safety concerns.

Based on these findings, the trial met its main goal and is showing promising signs of effectiveness for the combination therapy.

These results are encouraging when compared with those of the KEYNOTE-006 trial, Bjørheim said, which found 68% of advanced melanoma patients first treated with Keytruda alive after one year, and these people lived without signs of disease progression for a median of 11.6 months.

Ultimovacs plans to present detailed information from the first patient group at an oncology conference in the first half of 2021, while one-year results from the second group will be available in the second half.

Carlos de Sousa, Ultimovacs’ CEO, said that these top-line data “complement our extensive and growing clinical data package, confirming that this strong safety profile holds when combining UV1 with a PD-1 checkpoint inhibitor.”

These findings add to results from a previous Phase 1/2a trial (NCT02275416) in metastatic melanoma patients, in which UV1 was combined with the CTLA-4 checkpoint inhibitor Yervoy (ipilimumab; by Bristol-Myers Squibb).

In both trials, combination treatment was well tolerated, providing a solid basis for the triple combination of UV1 with CTLA-4 and PD-1 checkpoint inhibitors, which is currently being investigated in the company’s INITIUM (NCT04382664) and NIPU (NCT04300244) Phase 2 trials.

INITIUM is evaluating the safety and effectiveness of first-line treatment with UV1, in combination with Yervoy and Opdivo (nivolumab) — Bristol-Myers Squibb’s PD-1 checkpoint inhibitor — in up to 154 adults with metastatic, inoperable melanoma. Patients are being recruited at clinical sites across the U.S. and Europe; information on contacts and locations can be found here.

NIPU will test the triple combo as a second-line treatment in up to 118 adults with malignant pleural mesothelioma, a rare but aggressive cancer that affects the lungs’ protective lining tissue. Patient enrollment is ongoing in Europe and Australia; information can be found here.

Ultimovacs, in collaboration with a pharmaceutical company and a European oncology clinical trial group, plans to also launch a third Phase 2 trial testing a different UV1 combination therapy in a new cancer indication.

“We look forward to announcing the collaboration and trial timelines during the fourth quarter,” said de Sousa.