In July 2024 BioNTech announced positive topline data from its ongoing Phase II trial in patients with unresectable stage III or IV melanoma whose disease had progressed after anti-PD-(L)1-containing treatment. The trial evaluates the clinical activity and safety of BioNTech’s investigational mRNA cancer immunotherapy, BNT111, in combination with Libtayo (cemiplimab), Regeneron’s anti-PD-1 monoclonal antibody, and assesses the two single agents alone.
Melanoma
BioNTech states that melanoma is among the leading causes of cancer-related deaths across the world; it is responsible for around 58,000 deaths each year. Anti-PD-1 refractory/relapsed unresectable stage III or IV melanoma is an “aggressive form” that “remains particularly lethal”. Although checkpoint inhibitor therapies “substantially improve the life expectancy” of many patients, others exhibit resistance to approved therapies.
“The 5-year survival rate for patients with distant metastatic melanoma is approximately 35%. This underscores the significant unmet medical need.”
BNT111 in trial
BNT111 is an mRNA-based off-the-shelf cancer immunotherapy candidate for intravenous administration, which encodes a fixed set of four non-mutated melanoma-associated antigens (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE), delivered as uridine mRNA-lipoplex formulation. More than 90% of patients with cutaneous melanoma express “at least one” of these antigens.
The trial, BNT111-01, is an open-label, randomised Phase II trial to evaluate the efficacy of BNT111 and cempilimab and the contribution made by each component in patients with anti-PD-1/PD-L1-refractory or relapsed, unresectable stage III or IV cutaneous melanoma. It takes place across around 60 sites in 7 countries and seeks to demonstrate anti-tumour activity and overall response rate (ORR) of the combination and each agent alone. Other endpoints include duration of response (DOR), disease control rate (DCR), overall survival (OS), safety, and tolerability.
A significant step
The trial met its primary efficacy outcome measure, demonstrating a “statistically significant improvement” in ORR in patients who received the combination treatment compared to historical control in this indication and treatment setting. Both randomised monotherapy arms showed clinical activity. The combination approach had a safety profile that was consistent with previous trials. The trial will continue as planned to further assess secondary endpoints.
Professor Özlem Türeci, Chief Medical Officer and Co-Founder of BioNTech, is pleased with the “significant step towards our vision of personalised cancer medicine”.
“We envision mRNA as a centrepiece in future treatment paradigms for cancer, helping to address unmet medical needs, such as for patients with anti-PD-(L)1 refractory or resistant melanoma.”
The data serve Professor Türeci and team in “three dimensions”:
“First, for our decade-long improved mRNA cancer vaccine technology that uses uridine mRNA chemistry, a non-coding backbone that is engineered for optimal translational performance and our proprietary lipoplex formulation for delivery. Second, for our computational approaches for selecting suitable tumour antigens for our cancer indication-specific FixVac platform candidates. Third, for our strategy to combine synergistic modalities, in this case BNT111 with an established immune checkpoint treatment.”
To hear more from BioNTech about their cancer vaccine progress, join us at the Congress in Barcelona this October. Don’t forget to subscribe to our newsletters here for weekly vaccine insights.
Trackbacks/Pingbacks