Abstract CT108: Phase I data from TENDU101, a first-in-human trial of a novel synthetic peptide conjugate cancer vaccine platform assessed in recurrent prostate cancer patients before salvage treatment
Authors: Lilleby Wolfgang , Bergqvist Anna , Nasi Aikaterini , Rasch Wenche , Mangsbo Sara 
Published: April 2024

Abstract
Synthetic peptides are explored in the clinic in cancer vaccine development for the purpose of inducing tumor-directed T cell responses. Their immunogenicity is dependent on the chosen adjuvant and target organ exposure (lymphoid organs). To improve peptide immunogenicity, we have developed a technology enabling cross-linking of endogenous, pre-existing circulating antibodies (Abs) by employing a three-dimensional chemistry design. Multiple identical tetanus toxin-derived B cell epitopes (MTTEs) are conjugated to synthetically made antigenic tumor peptides intended to induce T cell responses. Here we report the first clinical safety assessment of the vaccine platform in the trial TENDU101 (NCT04701021). The cancer vaccine candidate (TENDU) was designed to include longer synthetic peptides harboring prostate cancer derived epitopes (CD4 and CD8) from PAP and PSMA. The study was a 3+3 design and doses were 40, 400 and 960 microgram in patients with documented recurrent disease after radical prostatectomy. A tetanus toxoid (TTd) containing vaccine boost was followed by TENDU vaccination via subcutaneous injection in the abdomen (4 doses in total with a 2 week interval) in n=9 patients (gr 1, 2, 3.1). For group 3.2 (n=3) TENDU vaccination was administrated in the same arm as the TTd vaccination. Primary objective was safety and secondary objective assessment of immune responses and preliminary anti-tumor responses. A total of 52 adverse events (AEs) were reported, most mild and deemed unrelated to vaccination. Six treatment-related AEs were reported of which 50% were mild transient injection site reactions in a single patient (gr 3.1), and three events of increases in lipase levels in two patients (gr 2). No serious AEs was reported. T cell responses pre/post TENDU were assessed in a total of six patients of which five patients displayed increased response against vaccine-related CD8 and CD4 epitopes (ELISpot). The three patients with the greatest increase in T cell responses were found to display the highest anti-MTTE IgG responses. A trend towards decrease in circulating tumor cells from screening to the end of treatment visit was observed in the patients with the highest levels of anti-MTTE IgGs post TENDU vaccination. There were no trends for decrease in PSA and/or PAP at the end of treatment and follow-up measurements were affected by initiation of radiation and short-term androgen deprivation. The administration of TTd and TENDU to the same anatomical location although spaced in time appeared to negatively influence immune responses to TTd and TENDU. In conclusion, the novel synthetic peptide conjugate vaccine conjugate was found safe with no serious AEs reported and a positive correlation between anti-MTTE and T cell responses was noted in patients when TENDU was administrated in the abdomen.
Citation Format: Wolfgang Lilleby, Anna Bergqvist, Aikaterini Nasi, Wenche Rasch, Sara Mangsbo. Phase I data from TENDU101, a first-in-human trial of a novel synthetic peptide conjugate cancer vaccine platform assessed in recurrent prostate cancer patients before salvage treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT108.