421 A first-in-human (FIH) phase I/IIa clinical trial assessing a ribonucleic acid lipoplex (RNA-LPX) encoding shared tumor antigens for immunotherapy of prostate cancer; preliminary analysis of PRO-MERIT

Background PRO-MERIT is a FIH, open-label, multicenter, Phase I/IIa trial investigating liposomal RNA vaccine (BNT112) targeting the prostate cancer tumor-associated antigens (TAAs) kallikrein-2, kallikrein-3, acid phosphatase prostate, homeobox B13 (HOXB13), and NK3 1. BNT112 being investigated as monotherapy in combination with cemiplimab patients metastatic castration-resistant (mCRPC) newly diagnosed high risk localized (LPC). Methods The involves dose titration mCRPC (who have progressed after at least 2 but no more than 3 lines of systemic therapy) (Part 1, fully recruited), followed by expansion cohorts 2, recruiting) both mCPRC LPC either or cemiplimab. Primary endpoints investigate safety, tolerability, preliminary anti-tumor activity (by Prostate Cancer Working Group criteria). Secondary include determination induction antigen-specific T cells. Vaccine-induced immune responses are analyzed ex vivo using an interferon-γ enzyme-linked absorbent spot (ELISpot) assay following short-term vitro stimulation. Results As 17 May 2021, 11 received (9 Part 1; 2) (at one cycle completed). In all 9 were stage IV diagnosis receiving androgen deprivation therapy. Median age was 68 years. Two out experienced Grade hypertension, leading to reduction, that initially reported dose-limiting toxicity (DLT). All recovered within 24 h sequelae Safety Review Committee eventually concluded events did not meet DLT definition. Most common related adverse (AEs) pyrexia hypertension. Eight serious AEs 5 patients, unrelated BNT112. additional safety signals concerns identified date, ELISpot data showed vaccine-induced present 7/7 ELISpot-evaluable patients. TAAs found be immunogenic. Responses each antigen observed subjects. Initial decreased prostate-specific (PSA) levels been arm. Conclusions These suggest has acceptable profile. Additionally, induces robust PSA advanced cancer. Acknowledgements authors would like acknowledge Camilla West (BioNTech SE) for medical writing support. Trial Registration Clinicaltrials. gov: NCT04382898 . Ethics Approval & Institutional Board approvals obtained from respective participating countries prior initiation trial.