Abstract 3297
Background
Most therapeutic vaccine clinical trials (CTs) have failed to prove efficacy, even if immunogenicity was confirmed earlier. It was already shown that immune responses generated against multiple antigens are indicative of clinical responses. We aimed to find association between the heterogeneity of immune response and clinical efficacy and, based on this develop a tool that can predict the clinical outcome of cancer vaccines.
Methods
In an extensive literature search we collected the immune- and objective response rates (IRR, ORR) of 94 CTs in which 2,338 patients were treated with 64 different vaccines. Vaccine sequences were used to predict personal epitopes (PEPIs) that bind to at least 3 HLA alleles of the same subject, for all patients of a representative model population. Then we determined the percentage of subjects with at least 1 vaccine specific PEPIs (PEPI Score) and at least 2 vaccine specific PEPIs derived from different antigens (MultiAg PEPI-Score) and compared to the published IRR and ORR.
Results
PEPI Score was able to predict the immunogenicity of therapeutic vaccines; significant correlation was found with IRR (p = 0.002). As expected, no correlation was found between ORR and IRR (p = 0.294), neither between PEPI Score and ORR (p = 0.302), suggesting, that immune response against a single epitope is not enough for efficient tumor response. However, we found that MultiAg PEPI-Score significantly correlates with ORR (p < 0.0001) consistent with earlier findings that the targeting of multiple antigens is required for tumor shrinkage.
Conclusions
Our results demonstrate that both IRR and ORR can be predicted by PEPIs. For clinical efficacy it is crucial to target and generate immune response against multiple antigens. Based on our analysis our computational model is useful and accurate for the prediction of the clinical outcome of cancer vaccines and can even be suitable for rescuing CTs with insufficient or missing responder selection.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
O. Lorincz: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. J. Toth: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. M. Megyesi: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. K. Pántya: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. E. Somogyi: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. Z. Csiszovszki: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. P. Pales: Full / Part-time employment: Treos Bio Zrt. L. Molnar: Shareholder / Stockholder / Stock options: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. E.R. Tőke: Shareholder / Stockholder / Stock options, Officer / Board of Directors: Treos Bio Ltd; Full / Part-time employment: Treos Bio Zrt. All other authors have declared no conflicts of interest.
Resources from the same session
5650 - Tissue-based activation of mucosal-associated invariant T (MAIT) cells in combination ipilimumab and nivolumab checkpoint inhibitor (CI) colitis.
Presenter: Sarah Sasson
Session: Poster Display session 3
Resources:
Abstract
5944 - Significance of severe immune-related adverse effects (irAE) on patients with advanced tumors treated with immune checkpoint inhibitors being admitted for secondary toxicity: Clinical relevance and next steps
Presenter: Leyre Zubiri
Session: Poster Display session 3
Resources:
Abstract
5989 - Implementation of a dedicated immuno-oncology toxicity service reduces the acute impact of immune-related adverse events
Presenter: Anna Olsson-Brown
Session: Poster Display session 3
Resources:
Abstract
3267 - Cardiotoxic and pro-inflammatory effects induced by the association of immune checkpoint inhibitor Pembrolizumab and Trastuzumab in preclinical models
Presenter: Nicola Maurea
Session: Poster Display session 3
Resources:
Abstract
3417 - Interstitial lung disease associated with immune-checkpoint inhibitors in malignant diseases
Presenter: Akira Yamagata
Session: Poster Display session 3
Resources:
Abstract
2071 - A Phase 1 Study of Intraperitoneal MCY-M11 Anti-Mesothelin CAR for Women with Platinum Resistant High Grade Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube, or Subjects with Peritoneal Mesothelioma with Recurrence after Prior Chemotherapy
Presenter: Christina Annunziata
Session: Poster Display session 3
Resources:
Abstract
4935 - Trial in progress: First-in-human study of a novel anti-NY-ESO-1–anti-CD3, TCR-based bispecific (IMCnyeso) as monotherapy in NY-ESO-1/LAGE-1A-positive advanced solid tumors (IMCnyeso-101)
Presenter: Juanita Lopez
Session: Poster Display session 3
Resources:
Abstract
5613 - Nimotuzumab-Cisplatin-Radiation versus Cisplatin-Radiation in HPV negative oropharyngeal cancer
Presenter: Kumar Prabhash
Session: Poster Display session 3
Resources:
Abstract
2576 - Interim analysis of a single arm phase 2 study of adjuvant nivolumab after salvage resection in head and neck squamous cell carcinoma patients previously treated with definitive therapy.
Presenter: Trisha Wise-draper
Session: Poster Display session 3
Resources:
Abstract
4758 - A Phase I Study of the CDK4/6 Inhibitor, Palbociclib in combination with Cetuximab and Intensity Modulated Radiation Therapy (IMRT) for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN); A Result of Dose Escalation Cohort
Presenter: Nuttapong Ngamphaiboon
Session: Poster Display session 3
Resources:
Abstract