BioNTech Announces Promising Phase 2 Results for mRNA Immunotherapy BNT111 in Advanced Melanoma
BioNTech today revealed positive topline data from its ongoing Phase 2 clinical trial (EudraCT No.: 2020-002195-12; NCT04526899) involving patients with unresectable stage III or IV melanoma whose disease had progressed despite anti-PD-(L)1 treatment. This randomized trial investigates the clinical activity and safety of the investigational mRNA cancer immunotherapy BNT111 in combination with Libtayo® (cemiplimab), an anti-PD-1 monoclonal antibody developed by Regeneron, as well as evaluating each agent alone.
The trial met its primary efficacy endpoint, showing a statistically significant improvement in overall response rate (ORR) for patients treated with BNT111 plus cemiplimab compared to historical controls. Both monotherapy arms also exhibited clinical activity. The ORR for the cemiplimab monotherapy was consistent with historical data for anti-PD-(L)1 or anti-CTLA-4 treatments in this patient population. The treatment was well tolerated, with the safety profile of BNT111 combined with cemiplimab aligning with previous studies. The Phase 2 trial will proceed to further evaluate secondary endpoints, which were not yet mature during the primary analysis.
Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech, commented, “These Phase 2 results are a significant milestone in our quest for personalized cancer medicine. We believe mRNA will be central to future cancer treatments, addressing unmet needs for patients with anti-PD-(L)1 refractory or resistant melanoma. These results validate our advanced mRNA cancer vaccine technology, our approach to selecting tumor antigens, and our strategy of combining complementary therapies.”
BioNTech and Regeneron plan to present the trial data at an upcoming medical conference and aim to publish the findings in a peer-reviewed journal.
BNT111, developed from BioNTech’s proprietary FixVac platform, uses a fixed combination of four mRNA-encoded tumor-associated antigens to elicit a targeted immune response against cancer cells. In 2021, BNT111 in combination with cemiplimab received Fast Track designation from the FDA for treating anti-PD-1-refractory or relapsed, unresectable stage III or IV melanoma, and Orphan Drug designation for treating stage IIB through IV melanoma.
About BioNTech’s Oncology mRNA Platforms
BioNTech is advancing several mRNA platforms to create novel therapies and vaccines. In oncology, BioNTech employs five mRNA platforms. The FixVac platform targets specific cancer indications with shared tumor-associated antigens, while the iNeST platform offers personalized immunotherapies based on individual tumor profiles. Both platforms use BioNTech’s proprietary uridine mRNA technology and lipoplex delivery technology. Currently, six programs from these platforms are in Phase 2 trials for various solid tumors.
In addition, BioNTech is using mRNA for targeted antibody, cytokine, and immunomodulating protein therapies through its RiboMab, RiboCytokine, and Intratumoral Immunotherapy platforms.
About Advanced Melanoma
Melanoma is a leading cause of cancer-related deaths, with about 58,000 deaths annually. Anti-PD-1 refractory or relapsed unresectable stage III or IV melanoma is particularly aggressive. Current treatments, such as checkpoint inhibitors, improve survival but many patients develop resistance, leading to limited options. The 5-year survival rate for distant metastatic melanoma is approximately 35%, highlighting the critical need for new treatments.
About BNT111
BNT111 is an mRNA-based immunotherapy candidate encoding four melanoma-associated antigens (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE) delivered as a uridine mRNA-lipoplex formulation. It is designed to induce immune responses against these antigens, which are expressed by over 90% of cutaneous melanomas. Previous Phase 1 trials have demonstrated that BNT111, alone or combined with PD-1 blockade, can elicit and enhance immune responses in melanoma patients. BNT111 is currently in a Phase 2 trial evaluating its effectiveness in combination with cemiplimab.
About the BNT111-01 Trial
The BNT111-01 trial (EudraCT No.: 2020-002195-12; NCT04526899) is an open-label, randomized Phase 2 trial assessing BNT111 and cemiplimab, as well as each component individually, in patients with anti-PD-1/PD-L1-refractory or relapsed, unresectable stage III or IV melanoma. Conducted at approximately 60 sites across 7 countries, the trial aims to evaluate anti-tumor activity, ORR, duration of response, disease control rate, overall survival, safety, and tolerability.
About BioNTech
BioNTech is a global leader in next-generation immunotherapy, developing novel treatments for cancer and other serious diseases. Its diverse portfolio includes individualized and off-the-shelf mRNA therapies, CAR T cells, protein-based therapeutics, and small molecules. BioNTech also collaborates with various global pharmaceutical companies to advance its mRNA vaccine candidates for infectious diseases and its oncology pipeline.
