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
3489 - Overall Survival (OS) and Metastasis-Free Survival (MFS) in men with Biochemically Relapsed (BCR) Prostate Cancer after radical prostatectomy (RP) managed with deferred Androgen Deprivation Treatment (ADT): A combined Johns Hopkins and CPDR study
Presenter: Catherine Marshall
Session: Poster Display session 3
Resources:
Abstract
4606 - ARCHES – the role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of high and low disease volume and risk groups
Presenter: Arnulf Stenzl
Session: Poster Display session 3
Resources:
Abstract
2975 - Updated survival analyses of a multicentric phase II randomized trial of docetaxel (D) plus enzalutamide (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (CHEIRON study).
Presenter: Orazio Caffo
Session: Poster Display session 3
Resources:
Abstract
2708 - Real-world analysis of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving vs not receiving chemotherapy in the treatment sequence
Presenter: Alicia Morgans
Session: Poster Display session 3
Resources:
Abstract
2134 - Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial
Presenter: Janet Brown
Session: Poster Display session 3
Resources:
Abstract
3504 - Risk of falls and fractures in patients with castration resistant prostate cancer (CRPC) treated with new hormonal agents – a meta-analysis of randomized controlled trials.
Presenter: Rodrigo Coutinho Mariano
Session: Poster Display session 3
Resources:
Abstract
2342 - Pain progression at initiation of chemotherapy in metastatic Castration-Resistant Prostate Cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of FIRSTANA
Presenter: Nicolas Delanoy
Session: Poster Display session 3
Resources:
Abstract
5331 - Pain evaluation in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the PARABO observation study
Presenter: Holger Palmedo
Session: Poster Display session 3
Resources:
Abstract
2823 - Time to castration resistant prostate cancer (CRPC) and the risk of developing immune disorders
Presenter: Vincenza Conteduca
Session: Poster Display session 3
Resources:
Abstract
1500 - Retrospective evaluation of neutropenic admission events in metastatic or high-risk hormone-sensitive prostate cancer (HSPC) patients having docetaxel chemotherapy upfront or for castrate-resistant prostate cancer (CRPC) in STAMPEDE
Presenter: Harriet Mintz
Session: Poster Display session 3
Resources:
Abstract