4704 - Evaluation of safety, immunogenicity and preliminary efficacy of PolyPEPI1018 vaccine in subjects with metastatic colorectal cancer (mCRC) with a predictive biomarker

Background

This study evaluated the safety, tolerability, immunogenicity and initial efficacy of PolyPEPI1018 as an add-on to maintenance therapy in subjects with mCRC. PolyPEPI1018 peptide vaccine contains 12 unique epitopes derived from 7 conserved cancer antigens frequently expressed in mCRC. The predictive value of the novel Personal EPItopes (PEPI) test was also explored.

Methods

mCRC patients in first line setting received up to 3 doses of PolyPEPI1018 vaccine (0.2 mg/peptide) 12 weeks apart, just after the transition to maintenance therapy with fluoropyrimidine and bevacizumab. Vaccine-specific T cell responses were first predicted by PEPI test (using the patient’s complete HLA genotype) then measured by ELISpot and Intracellular Cytokine Staining (ICS) after one cycle of vaccination. Tumour responses were evaluated by RECIST.

Results

Eleven patients were vaccinated with PolyPEPI1018. The vaccine was well tolerated; common adverse events were transient skin reactions and flu-like syndrome. No grade 3+ adverse events related to the vaccine occurred. Initial analysis of 8 patients after a single dose demonstrated that 100% of patients had CD4+ T cell response and 75% had CD8+ T cell responses against at least 3 antigens. Both CD8+ and CD4+ T cells were polyfunctional based on the secretion of multiple cytokines determined by ex vivo ICS. PEPI test correctly predicted ELISpot-measured CD8+ T cell responses (PPV = 65%, p = 0.049). Of the 5 patients who received at least 2 doses of the vaccine, 3 experienced Stable disease and 2 had unexpected tumour size reduction. Patients experiencing tumour shrinkage had higher number of predicted antigens than those without tumour response.

Conclusions

PolyPEPI1018 was safe, well-tolerated and induced unprecedented broad polyfunctional CRC-specific T cell responses, similar to personalized neoantigen vaccines. The candidate biomarker demonstrated high accuracy for the prediction of subject’s vaccine-specific CD8+ T cell responses and indicated patient’s clinical responses. Based on these encouraging results further development of the PolyPEPI1018 vaccine with companion diagnostic is planned.

Clinical trial identification

NCT03391232.

Editorial acknowledgement

Legal entity responsible for the study

TreosBio.

Funding

Treos Bio.

Disclosure

J. Hubbard: Research grant / Funding (institution): Taiho Oncology; Research grant / Funding (institution): TreosBio; Advisory / Consultancy, Honoraria to Mayo Clinic: Bayer; Research grant / Funding (institution): Senhwa Pharmaceuticals; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Effector Therapeutics; Research grant / Funding (institution): Merck. E.R. Tőke: Full / Part-time employment: TreosBio. Z. Csiszovszki: Full / Part-time employment: TreosBio. O. Lorincz: Full / Part-time employment: TreosBio. L. Molnar: Full / Part-time employment: TreosBio. E. Somogyi: Full / Part-time employment: TreosBio. M. Megyesi: Full / Part-time employment: TreosBio. K. Pántya: Full / Part-time employment: TreosBio. J. Toth: Full / Part-time employment: TreosBio. P. Pales: Full / Part-time employment: TreosBio. I. Miklos: Full / Part-time employment: TreosBio. All other authors have declared no conflicts of interest.