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549 An RNA-lipoplex (RNA-LPX) vaccine demonstrates strong immunogenicity and promising clinical activity in a Phase I trial in cutaneous melanoma patients with no evidence of disease at trial inclusion
  1. Carmen Loquai1,
  2. Jessica Hassel2,
  3. Patrick Brück3,
  4. Evelyna Derhovanessian3,
  5. Katarina Cuk3,
  6. Verena Lörks3,
  7. Julian Sikorski3,
  8. Maike Gold3,
  9. Daniel Maurus3,
  10. Doreen Schwarck-Kokarakis3,
  11. Marion Kästner3,
  12. Thomas Weisenburger3,
  13. Ann-Kathrin Eller3,
  14. Sebastian Attig4,
  15. Silvana Hempel4,
  16. Petra Oehm3,
  17. Tana Omokoko3,
  18. Lena Kranz3,
  19. Juliane Quinkhardt3,
  20. Isabel Vogler3,
  21. Inga Liebig3,
  22. Stephanie Renken3,
  23. Melanie Leierer2,
  24. Verena Müller5,
  25. Heidrun Mitzel-Rink1,
  26. Matthias Miederer1,
  27. Stephan Grabbe1,
  28. Jochen Utikal6,
  29. Roland Kaufmann7,
  30. Ugur Sahin3 and
  31. Özlem Türeci3
  1. 1University Medical Center of the Johannes Gutenberg University, Mainz, Germany
  2. 2Heidelberg University Hospital, Mainz, Germany
  3. 3BioNTech, Mainz, Germany
  4. 4Translational Oncology Mainz (TRON), Mainz, Germany
  5. 5University of Heidelberg, Mainz, Germany
  6. 6German Cancer Research Center, Heidelberg, Germany
  7. 7University Hospital Frankfurt am Main, Frankfurt am Main, Germany


Background Lipo-MERIT is an ongoing, first-in-human, open-label, dose-escalation Phase I trial investigating safety, tolerability and immunogenicity of BNT111 in patients with advanced melanoma. BNT111 is an RNA-LPX vaccine targeting the melanoma tumor-associated antigens (TAAs) New York esophageal squamous cell carcinoma 1 (NY-ESO-1), tyrosinase, melanoma-associated antigen 3 (MAGE-A3), and transmembrane phosphatase with tensin homology (TPTE). A previous exploratory interim analysis showed that BNT111, alone or combined with immune checkpoint inhibition (CPI), has a favorable adverse event (AE) profile, gives rise to antigen-specific T-cell responses and induces durable objective responses in CPI-experienced patients with unresectable melanoma.1 Here, we present preliminary data in patients with no evidence of disease (NED) at trial inclusion in the BNT111 monotherapy subgroup.

Methods Patients with stage IIIB/C and IV pre-treated cutaneous melanoma were intravenously administered with BNT111 using a prime/repeat boost protocol. Patients were treated in seven dose escalation cohorts (7.2 to 400 µg total RNA) and three expansion cohorts to further explore dose levels of 14.4, 50 and 100 μg. In this analysis, patients receiving BNT111 monotherapy were grouped as having evidence of disease (ED) or NED, and immunogenicity, efficacy and safety were evaluated. Vaccine-induced immune responses were analyzed using an interferon-γ enzyme-linked immune absorbent spot (ELISpot) assay directly ex vivo.

Results As of May 24, 2021, 115 patients have received BNT111 within the Lipo MERIT trial. Of 71 patients treated with BNT111 monotherapy, 38 patients had ED and 33 patients had NED after prior therapies. Baseline characteristics were similar between the two groups. ELISpot data revealed comparable BNT111-induced T-cell responses against at least one TAA in ED vs. NED patients (14/22 [64%] and 19/28 [68%] patients with available ELISpot-evaluable samples, respectively), suggesting that BNT111 has the ability to induce T-cell immunity irrespective of the presence of a detectable tumor. As previously reported for ED patients, vaccine-induced CD4+ as well as CD8+ T-cell responses were also observed in NED patients, with a substantial fraction of de novo induced responses undetectable prior to vaccination. In NED patients, clinical efficacy was promising; median disease-free survival was 34.8 months (95% confidence interval: 7.0–not reached). The safety profile was similar in ED vs. NED patients; 38/38 (100%) and 32/33 (97%) patients experienced related treatment-emergent AEs, respectively, of which the majority were mild-to-moderate flu-like symptoms.

Conclusions Immunogenicity and safety profiles of BNT111 monotherapy were comparable in ED and NED patients. Promising signs of clinical activity were observed in NED patients.

Acknowledgements The authors would like to acknowledge Camilla West (BioNTech SE) for medical writing support.

Trial Registration Clinicaltrials.

gov: NCT02410733; EudraCT No. 2013-001646-33.


  1. Sahin U, Oehm P, Derhovanessian E, et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature 2020;585(7823):107–112.

Ethics Approval Ethics & Institutional Review Board approval was obtained prior to initiation of the trial (2018-13393_21-AMG federführend).

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