BioNTech SE announced positive topline results from its Phase 2 clinical trial evaluating BNT111, an mRNA cancer immunotherapy, in combination with Libtayo (cemiplimab) for patients with unresectable stage III or IV melanoma that has progressed following anti-PD-(L)1 treatment. The trial met its primary efficacy endpoint, demonstrating a statistically significant improvement in objective response rate (ORR) in patients treated with the combination compared to historical controls.
The randomized, open-label trial (EudraCT No.: 2020-002195-12; NCT04526899) assessed the clinical activity and safety of BNT111 in combination with cemiplimab, an anti-PD-1 monoclonal antibody developed by Regeneron, and evaluated each agent alone. The trial was conducted across approximately 60 sites in 7 countries.
Clinical Efficacy and Safety
The observed ORR in the cemiplimab monotherapy arm was consistent with historical data for anti-PD-(L)1 or anti-CTLA-4 treatments in this patient population. The combination therapy was well-tolerated, and the safety profile of BNT111 combined with cemiplimab was consistent with previous clinical trials involving BNT111 with anti-PD-(L)1-containing treatments. The study will continue to assess secondary endpoints.
"These Phase 2 results mark a significant step towards our vision of personalized cancer medicine," said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech. "These data are a proof of concept for us 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 tumor 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."
About BNT111 and the FixVac Platform
BNT111 is based on BioNTech’s FixVac platform, which utilizes a fixed combination of four mRNA-encoded, tumor-associated antigens (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE). It is designed to trigger an innate and tumor-antigen-specific immune response against cancer cells expressing one or more of these antigens. Over 90% of patients with cutaneous melanomas express at least one of these antigens.
In 2021, the FDA granted Fast Track designation for BNT111 in combination with cemiplimab for the treatment of anti-PD-1-refractory/relapsed, unresectable Stage III or IV melanoma. In the same year, the FDA also granted Orphan Drug designation for BNT111 for the treatment of stage IIB through IV melanoma.
Melanoma and Unmet Needs
Melanoma is a leading cause of cancer-related deaths globally, accounting for approximately 58,000 deaths annually. Anti-PD-1 refractory/relapsed unresectable Stage III or IV melanoma is particularly aggressive. While checkpoint inhibitor therapies have improved life expectancy, a significant proportion of patients exhibit resistance, leading to limited treatment options. The 5-year survival rate for patients with distant metastatic melanoma is approximately 35%, highlighting a substantial unmet medical need.
Trial Design
The BNT111-01 trial (EudraCT No.: 2020-002195-12; NCT04526899) is an open-label, randomized Phase 2 trial evaluating the efficacy of BNT111 and cemiplimab and the contribution of the single components in patients with anti-PD-1/PD-L1-refractory or relapsed, unresectable Stage III or IV cutaneous melanoma. Patients were randomized in a 2:1:1 ratio to Arm 1 (BNT111 + cemiplimab), Arm 2 (BNT111 monotherapy), and Arm 3 (cemiplimab monotherapy), with up to 24 months of active treatment. Additional endpoints include duration of response (DOR), disease control rate (DCR), overall survival (OS), safety, and tolerability.
