UV1 Vaccine Plus Pembrolizumab Shows Strong Safety, Early Activity in Metastatic Melanoma

Pipeline Report | <b>Pipeline Report: September 2021</b>

The universal cancer vaccine UV1 and granulocyte-macrophage colony-stimulating factor in combination with pembrolizumab elicited encouraging initial signs of clinical response with favorable safety and tolerability when used in the first-line treatment of patients with metastatic melanoma, meeting the primary end point of an ongoing phase 1 trial.

The universal cancer vaccine UV1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with pembrolizumab (Keytruda) elicited encouraging initial signs of clinical response with favorable safety and tolerability when used in the first-line treatment of patients with metastatic melanoma, meeting the primary end point of an ongoing phase 1 trial (NCT03538314).1

Topline results from the second cohort of 10 patients showed that the combination elicited an objective response rate (ORR) of 60%, with evidence of tumor shrinkage in 6 patients. Additionally, 3 patients had their tumors shrink to undetectable levels, translating to a complete response (CR) rate of 30%. These results were comparable to those reported in the first cohort of 20 patients examined on the same study.

Moreover, after 1 year, the overall survival (OS) rate was 90% in this cohort, and the median progression-free survival (PFS) had not yet been reached.

“The emerging picture is that the UV1/pembrolizumab combination has a strong safety profile and provides consistently high levels of clinical response in advanced melanoma,” Jens Bjørheim, chief medical officer of Ultimovacs ASA, stated in a press release. “These latest data add to the accumulating body of evidence demonstrating that UV1 is safe and can mobilize the immune system to play a transformative role in the treatment of solid tumors.”

To be eligible for enrollment, patients had to have unresectable histological confirmed stage IIIB, stage IIIC, or stage IV malignant melanoma, measurable disease per RECIST v1.1 criteria, and an ECOG performance status of 0 or 1.2 Patients could not have previously received pembrolizumab. Those with uveal or ocular malignant melanoma; those who received prior therapy with anti–CTLA-4, anti–PD-L1/L2, or oncolytic virus; and those with active brain metastases were excluded.3

Study participants were given 8 UV1 vaccinations at 300 μg with adjuvant GM-CSF. In cohort 1, 20 patients received 37.5 μg, as 10 patients in cohort 2 received 75 μg of GM-CSF. A total of 5 doses were administered during UV1 treatment. Pembrolizumab was continued per the label following completion of treatment with the vaccine.

The primary end point of the study is safety and tolerability, and secondary end points include ORR, OS, and PFS.

Among the 20 patients enrolled to cohort 1, 13 were male, the median age was 70 years (range, 31-82), 15 had an ECOG performance status of 0, 10 had stage IV disease, and 5 had elevated lactate dehydrogenase.

Results from cohort 1 of the study were presented during the 2021 ASCO Annual Meeting and showed an ORR of 60%, with a 30% CR rate and a 30% partial response rate. Additionally, median follow-up of 21.2 months, the combination yielded a survival rate of 80%, with a median PFS of 18.9 months.

Safety results from cohort 1 showed that all patients but 1 experienced an adverse effect (AE) with the combination. A total of 150 AEs were reported, and the majority were grade 1 (48%) or grade 2 (41%) in severity. Eighteen percent of toxicities were potentially/definitively linked with UV1 or pembrolizumab, respectively. Additionally, 3 patients reported a serious AE, with 1 SAE of inflammatory arthritis considered to be potentially associated with the vaccine. Notably, no severe allergic reactions were noted.

The phase 1 study is currently ongoing, and 2-year follow-up data from cohort 1 is expected to be shared later this year.

“These latest results are compelling, and in line with the data presented at ASCO from the first group of patients in this study,” Carlos de Sousa, chief executive officer of Ultimovacs, stated in a press release. “We will discuss these results further when we present the company’s Q2 2021 financial results to shareholders on August 20, 2021. We also plan to share more detailed results of the study at a major clinical oncology meeting in 2022.”

References

  1. Ultimovacs announces further positive topline results from phase I UV1 cancer vaccine combination study in metastatic melanoma. News release. Ultimovacs ASA. August 12, 2021. Accessed August 13, 2021. https://bit.ly/2Y6cQo5
  2. Zakharia Y, O’Day S, Rasch W, et al. A phase I clinical trial investigating the telomerase vaccine UV1 in combination with pembrolizumab in patients with advanced melanoma. J Clin Oncol. 2021;39(15):2620. doi:10.1200/JCO.2021.39.15_suppl.2620
  3. UV1 vaccine with pembrolizumab for patients with unresectable or metastatic melanoma. ClinicalTrials.gov. Updated May 25, 2021. Accessed August 13, 2021. https://clinicaltrials.gov/ct2/show/NCT03538314