1. Abstract Number - LBA9519

Title: Ultimovacs’UV1 Cancer Vaccine Fails to Improve Progression-Free Survival in Melanoma Trial

Commentary – Ultimovacs’ poster presentation at the ASCO will feature key findings and analysis after a minimum 18-month follow-up of the patients in the INITIUM trial.

Executive Summary – Ultimovacs is all set to present the data from the Phase II clinical trial INITIUM (NCT04382664), in a poster session at the 2024 ASCO Annual Meeting. Following the topline results announced in March 2024, detailed findings and analysis will be shared at the event.

Main Content – UV1 is an off-the-shelf therapeutic cancer vaccine that induces a specific T-cell response against telomerase. In March 2024, Ultimovacs announced topline results from the Phase II INITIUM clinical trial, which evaluates UV1 as a first-line treatment for unresectable or metastatic malignant melanoma. Despite not meeting the primary and secondary endpoints, Ultimovacs remains confident in UV1’s potential due to the encouraging results from previous trials and the broad diversity in the Phase II program. The company is committed to advancing toward the next significant data milestones.

The primary endpoint of the INITIUM study was to assess progression-free survival (PFS) in the experimental arm compared to the control arm. The experimental arm combined UV1 with the checkpoint inhibitors ipilimumab and nivolumab. Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DOR), and safety. Although the combination treatment showed similar clinical benefits, the study did not meet its primary and secondary endpoints.

The median PFS was not achieved in either arm, with a Hazard Ratio (HR) of 0.95 between the arms for PFS. While UV1 maintained a positive safety and tolerability profile, secondary endpoint evaluations revealed no significant differences in OS or ORR. Detailed results and analyses from the INITIUM trial will be presented at the ASCO Annual Meeting in Chicago on June 1, 2024.

Despite the disappointing results from the INITIUM trial in malignant melanoma, the NIPU trial in mesothelioma demonstrated a clinically meaningful improvement in overall survival for patients treated with UV1 alongside ipilimumab and nivolumab. Ultimovacs expects to receive more mature survival data from the NIPU trial in 2024. Additionally, results from the FOCUS trial in head and neck cancer are anticipated in Q3 2024, and results from the DOVACC trial in ovarian cancer are expected in H1 2025.

UV1 is designed as a convenient off-the-shelf product with a long shelf life, easy intradermal administration, and no need for patient pre-screening or sophisticated hospital infrastructure. These features enhance its accessibility, making it available to centers in rural and underserved communities, thereby ensuring broad patient access to therapy.

Conclusion: Ultimovacs' off-the-shelf therapeutic cancer vaccine UV1 triggers immune responses against telomerase, a protein in 85-90% of all cancer types at all tumor stages. The universal nature of this target supports a clinical development strategy aimed at evaluating UV1's potential across various cancer types and treatment combinations.

2. Abstract Number – LBA9512

Title: 3-year data update of mRNA-4157 from Merck/Moderna’s KEYNOTE-942 trial of mRNA-4157 + pembro vs. pembro in adjuvant melanoma at ASCO

Commentary - In a rapid oral session, the upcoming ASCO conference will cover a 3-year data update of mRNA-4157 plus pembrolizumab in resected melanoma from the KEYNOTE-942 trial. 

Executive Summary – The Phase IIb KEYNOTE-942/mRNA-4157-P201 trial, evaluating the combination of mRNA-4157 (V940) with KEYTRUDA in patients with high-risk stage III/IV melanoma, has continued to show impressive results so far. Updated with longer follow-ups this year, the data should be in line with initial disclosures last year.

Main Content – mRNA-4157 (V940), developed by Moderna in collaboration with Merck, is an individualized neoantigen therapy, effectively a personalized cancer vaccine that aims to harness a patient's immune system to target their cancer. The Phase II KEYNOTE-942 trial investigated the efficacy and safety of mRNA-4157 in combination with pembrolizumab (KEYTRUDA) compared to pembrolizumab alone in patients with high-risk stage III/IV melanoma following complete resection of their tumor.

Key findings from the December 2023 update of the KEYNOTE-942 trial include:

• The combination of mRNA-4157 and pembrolizumab reduced the risk of recurrence or death by 49% compared to pembrolizumab alone at three years follow-up.

• The combination therapy showed a 25% rate of grade 3 or higher treatment-related adverse events, whereas pembrolizumab alone had a 20% rate.

Additionally, Moderna's CEO, indicated in December 2023 that their experimental melanoma vaccine could be available as early as 2025, marking a significant advancement in the treatment of this severe form of skin cancer.

We anticipate that the updated data from the KEYNOTE-942 trial, to be presented at ASCO, will provide further insights with longer follow-up and should be in line with the initial disclosures from last year. This updated data will likely reinforce the combination's efficacy and safety profile, continuing to highlight the significant reduction in the risk of recurrence or death and providing more detailed information on treatment-related adverse events over an extended period.

Conclusion: Looking to replicate and build upon the success seen in the KEYNOTE-942 trial, Moderna is conducting a Phase III study of mRNA-4157 in over 1,000 patients with melanoma. This study includes patients with stage IIB and stage IIC melanoma, in addition to stage III/IV patients from KEYNOTE-942.

Even if the therapy does not show efficacy in stage II melanoma patients, but continues to demonstrate significant benefits in the stage III/IV melanoma subgroup, likely, regulatory approval for the latter indication would likely not be delayed. The efficacy in the more advanced stages of melanoma would still support the therapy’s approval for those patients, potentially paving the way for a targeted approach to treating high-risk melanoma.