924P - Polyfunctional HPV16-Specific T cell responses in subjects receiving PDS0101 and pembrolizumab combination treatment for recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC)

Background

Generation of multifunctional, anti-tumor T cell responses and immune memory are critical to effective long term control of tumor growth and clinical outcomes. The investigational T cell activating HPV-targeted immunotherapy PDS0101 is being studied in combination with pembrolizumab (NCT04260126) in patients with HPV16-positive head and neck cancer. Biomarkers of response are undetermined.

Methods

The Isoplexis IsoCode single-cell proteomic assay was utilized to assess the functional state of tumor-specific CD4 and CD8 T cells. Cryopreserved PBMCs were thawed and rested overnight in the presence of IL-2, with magnetic bead column enrichment and surface staining for CD8/CD4 subsets following in vitro stimulation for 16 hrs with an overlapping HPV16 E6/E7 peptide pool. Single-cell production of 32 immune analytes was measured and polyfunctionality was assessed at 3 timepoints: pre-treatment, and 12 and 36 weeks following 4 and 5 cycles of combination therapy, respectively.

Results

Eighteen subjects with confirmed HPV16-positive tumors and CPS ≥1 (72% with CPS ≥20), median age 63 yrs (range 46-83), 94% male, 94% immune checkpoint inhibitor (ICI)-naïve, had specimens for this analysis and had received a minimum of 4 cycles of combination therapy. Confirmed objective response (OR; 1 CR and 5PR) was seen in 6 subjects (33%); 10 subjects (56%) had SD and 2 subjects had PD (11%). Polyfunctional T cells expressing 2-5+ proteins were observed in subjects with CPS 1-19 and CPS ≥ 20 and in both CD4 and CD8 subsets. Across timepoints and subjects, the proteins secreted with the highest frequency were Granzyme B, IL-8, IL-9, MIP-1α, MIP-1β and TNFα. There was no difference in polyfunctionality scores in subjects with confirmed OR versus those with stable or progressive disease.

Conclusions

The PDS0101/pembrolizumab combination generates polyfunctional CD4 and CD8 T cells that secrete multiple cytokines and chemokines associated with a predominant effector, stimulatory functional profile. Further investigation of T cell polyfunctionality and correlation with clinical outcomes is warranted.

Clinical trial identification

NCT04260126.

Editorial acknowledgement

Legal entity responsible for the study

PDS Biotechnology.

Funding

PDS Biotechnology.

Disclosure

K.J. Harrington: Financial Interests, Institutional, Principal Investigator: PDS Biotechnology. J. Weiss: Financial Interests, Personal and Institutional, Principal Investigator, Speaker, Consultant, Advisor: PDS Biotechnology. K. Price: Financial Interests, Institutional, Principal Investigator: PDS Biotechnology. J. Kaczmar: Financial Interests, Institutional, Principal Investigator: PDS Biotechnology. D. Schaaf, N. Riebel, S. Jones: Financial Interests, Personal, Full or part-time Employment: PDS Biotechnology. A. Cotty, S.G. McCarthy: Financial Interests, Institutional, Financially compensated role, Contract Laboratory Services: PDS Biotechnology. L.V. Wood: Financial Interests, Personal, Full or part-time Employment: PDS Biotechnology.