Is There a Role for Immunotherapy in Prostate Cancer?
Abstract
:1. Introduction
2. Predictive Biomarkers: PD-L1, MSI, MMR, TMB, DDR, TILs
3. Prostate Cancer Vaccines
4. Single Agent Immune Checkpoint Inhibitors Trials
5. Combination Immune Checkpoint Inhibitors Trials
6. Conclusions
Funding
Conflicts of Interest
Abbreviations
APCs | antigen-presenting cells |
CDK12 | Cyclin-Dependent Kinase 12 |
CTLA-4 | cytotoxic T-lymphocyte antigen-4 |
DCs | dendritic cells |
DDR | DNA damage repair |
GM-CSF | granulocyte-macrophage colony stimulating factor |
dMMR | mismatch repair deficiency |
HR | homologous recombination |
HRD | homologous recombination deficiency |
ICAM-1 | intercellular adhesion molecule 1 |
irAEs | immune-related adverse events |
LFA-3 | lymphocyte function-associated antigen 3 |
LLO | listeriolysin O |
LM | listeria monocytogenes |
mCRPC | metastatic castration-resistant prostate cancer |
MDSCs | myeloid-derived suppressor cells |
mHSPC | metastatic hormone sensitive prostate cancer |
MSI-H | high microsatellite instability |
Mut/Mb | mutations/megabase |
nmHSPC | non-metastatic hormone sensitive prostate cancer |
ORR | overall response rate |
OS | overall survival |
PAP | prostatic acid phosphatase |
PARPi | poly ADP ribose polymerase inhibitor |
PC | prostate cancer |
PD-1 | programmed death receptor 1 |
PFS | progression-free survival |
PSA | Prostate Specific Antigen |
PSADT | PSA doubling time |
RECIST | Response Evaluation Criteria in Solid Tumors |
RP | radical prostatectomy |
rPFS | progression-free survival rate |
SBRT | stereotactic body radiation therapy |
TILs | tumor infiltrating lymphocytes |
TMB | tumor mutational burden |
TRICOM | TRIad of CO-stimulatory Molecules |
TRAEs | treatment-related adverse events |
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NCT (clinicaltrials.gov) | Phase | Setting | Number of Patients | Experimental Arm | Control Arm | Mechanism of Action | Status |
---|---|---|---|---|---|---|---|
NCT03170960 | I/II | mCRPC | 1732 | Atezolizumab + Cabozantinib | \ | Atezolizumab: anti-PD-L1 Cabozantinib: tyrosine kinase inhibitor | Recruiting |
NCT03673787 | I/II | mCRPC (PTEN loss) | 51 | Atezolizumab + Ipatasertib | \ | Atezolizumab: anti-PD-L1 Ipatasertib: inhibitor of the serine/threonine protein kinase Akt | Active, not recruiting |
NCT03024216 | I | mCRPC | 37 | Atezolizumab + Sipuleucel-T | \ | Atezolizumab: anti-PD-L1 Sipuleucel-T: autologous cellular immunotherapy | Active, not recruiting |
NCT02655822 | I | mCRPC | 336 | Atezolizumab + Ciforadenant | \ | Atezolizumab: anti-PD-L1 Ciforadenant: inhibitor of the adenosine A2A receptor | Recruiting |
NCT02788773 | II | mCRPC | 52 | Durvalumab +/− Tremelimumab | \ | Durvalumab: anti-PD-L1 Tremelimumab: anti-CTLA-4 | Active, not recruiting |
NCT03204812 | II | mCRPC | 27 | Durvalumab + Tremelimumab | \ | Durvalumab: anti-PD-L1 Tremelimumab: anti-CTLA-4 | Active, not recruiting |
NCT02643303 | I/II | mCRPC | 102 | Durvalumab + Tremelimumab + PolylCLC | \ | Durvalumab: anti-PD-L1 Tremelimumab: anti-CTLA-4 PolylCLC: tool-like receptor agonist | Recruiting |
NCT03385655 | II | mCRPC | 500 | Durvalumab + Tremelimumab | Carboplatin or Ipatasertib or Savolitinib or Darolutamide or Adavosertib or CFI-400945 | Durvalumab: anti-PD-L1 Tremelimumab: anti-CTLA-4 Carboplatin: platinum salt Ipatasertib: AKT inhibitor Savolitinib: cMET inhibitor Darolutamide: non-steroidal androgen receptor antagonist Adavosertib: WEE-1 inhibitor CFI400945: PLK4 inhibitor | Recruiting |
NCT02740985 | I | mCRPC | 307 | Durvalumab + AZD4635 | \ | Durvalumab: anti-PD-L1 AZD4635: antagonist of the adenosine A2A receptor | Recruiting |
NCT03330405 | II | mCRPC | 214 | Avelumab + Talazoparib | \ | Avelumab: anti-PD-L1 Talazoparib: PARP inhibitor | Active, not recruiting |
NCT03409458 | I/II | mCRPC | 52 | Avelumab + PT-112 | \ | Avelumab: anti-PD-L1 PT-112: A platinum agent complexed to a pyrophosphate ligand | Recruiting |
NCT02933255 | I/II | Cohort 1: mCRPC Cohort 2: localized prostate cancer | 29 | Nivolumab +/− PROSTVAC-V/F | \ | Nivolumab: anti-PD-1 PROSTVAC-V/F: A vaccine composed of rilimogene galvacirepvec (a recombinant vaccinia virus) and rilimogene glafolivec (a recombinant fowlpox virus) | Recruiting |
NCT03600350 | II | nmHSPC | 41 | Nivolumab + pTVG-HP | \ | Nivolumab: anti-PD-1 pTVG-HP: A vaccine containing plasmid DNA encoding human prostatic acid phosphatase | Recruiting |
NCT03572478 | I/II | mCRPC | 12 | Nivolumab + Rucaparib | \ | Nivolumab: anti-PD-1 Rucaparib: PARP inhibitor | Active, not recruiting |
NCT03040791 | II | mCRPC (DDR defects) | 29 | Nivolumab | \ | Nivolumab: anti-PD-1 | Recruiting |
NCT03338790 | II | mCRPC | 330 | Nivolumab + Rucaparib or Docetaxel or Enzalutamide | \ | Nivolumab: anti-PD-1 Rucaparib: PARP inhibitor Docetaxel: taxane Enzalutamide: androgen receptor targeted agent | Recruiting |
NCT03061539 | II | mCRPC (dMMR, DDR defects, high TILs) | 175 | Nivolumab + Ipilimumab | \ | Nivolumab: anti-PD-1 Ipilimumab: anti-CTLA-4 | Recruiting |
NCT03570619 | II | mCRPC (biallelic CDK12 loss) | 40 | Nivolumab + Ipilimumab | \ | Nivolumab: anti-PD-1 Ipilimumab: anti-CTLA-4 | Recruiting |
NCT03532317 | I | mCRPC | 20 | Neoantigen DNA Vaccine + Nivolumab/Ipilimumab + PROSTVAC-V/F | \ | Nivolumab: anti-PD-1 Ipilimumab: anti-PD-L1 PROSTVAC-V/F: A vaccine composed of rilimogene galvacirepvec (a recombinant vaccinia virus) and rilimogene glafolivec (a recombinant fowlpox virus) | Recruiting |
NCT02985957 | II | mCRPC | 497 | Nivolumab/Ipilimumab or Ipilimumab | Cabazitaxel | Nivolumab: anti-PD-1 Ipilimumab: anti-PD-L1 Cabazitaxel: microtubule inhibitor | Recruiting |
NCT04109729 | IB/II | mCRPC | 36 | Nivolumab + Radium-223 | \ | Nivolumab: anti-PD-1 Radium-223: alpha particle-emitting radiotherapy drug | Recruiting |
NCT01688492 | I/II | mCRPC | 57 | Ipilimumab + Abiraterone Acetate + prednisone | \ | Ipilimumab: anti-CTLA-4 Abiraterone Acetate: androgen receptor targeted agent | Active, not recruiting |
NCT03093428 | II | mCRPC | 45 | Pembrolizumab + Radium-223 | \ | Pembrolizumab: anti-PD-1 Radium-223: alpha particle-emitting radiotherapy drug | Active, not recruiting |
NCT03506997 | II | mCRPC | 100 | Pembrolizumab | \ | Pembrolizumab: anti-PD-1 | Recruiting |
NCT03248570 | II | mCRPC (with or without DDR defects) | 50 | Pembrolizumab | \ | Pembrolizumab: anti-PD-1 | Recruiting |
NCT02499835 | I/II | mCRPC | 72 | Pembrolizumab + pTVG-HP | \ | Pembrolizumab: anti-PD-1 pTVG-HP: A vaccine containing plasmid DNA encoding human prostatic acid phosphatase | Recruiting |
NCT02998567 | I | mCRPC | 34 | Pembrolizumab + guadecitabine | \ | Pembrolizumab: anti-PD-1 Guadecitabine: dinucleotide antimetabolite of a decitabine linked via phosphodiester bond to a guanosine | Active, not recruiting |
NCT03406858 | II | mCRPC | 33 | Pembrolizumab + HER2Biarmed activated T-cells | \ | Pembrolizumab: anti-PD-1 HER2Biarmed activated T-cells | Recruiting |
NCT03834493 | III | mCRPC | 1200 | Pembrolizumab + Enzalutamide | Enzalutamide + Placebo | Pembrolizumab: anti-PD-1 Enzalutamide: androgen receptor targeted agent | Recruiting |
NCT03473925 | II | mCRPC | 120 | Pembrolizumab + Navarixin | \ | Pembrolizumab: anti-PD-1 Navarixin: antagonist of CXCR1 and CXCR2 | Active, not recruiting |
NCT03007732 | II | mHSPC | 42 | Pembrolizumab + SBRT +/− SD-101 | \ | Pembrolizumab: anti-PD-1 SD-101: synthetic CpG oligonucleotide that stimulates Toll-like receptor 9 | Recruiting |
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Rizzo, A.; Mollica, V.; Cimadamore, A.; Santoni, M.; Scarpelli, M.; Giunchi, F.; Cheng, L.; Lopez-Beltran, A.; Fiorentino, M.; Montironi, R.; et al. Is There a Role for Immunotherapy in Prostate Cancer? Cells 2020, 9, 2051. https://doi.org/10.3390/cells9092051
Rizzo A, Mollica V, Cimadamore A, Santoni M, Scarpelli M, Giunchi F, Cheng L, Lopez-Beltran A, Fiorentino M, Montironi R, et al. Is There a Role for Immunotherapy in Prostate Cancer? Cells. 2020; 9(9):2051. https://doi.org/10.3390/cells9092051
Chicago/Turabian StyleRizzo, Alessandro, Veronica Mollica, Alessia Cimadamore, Matteo Santoni, Marina Scarpelli, Francesca Giunchi, Liang Cheng, Antonio Lopez-Beltran, Michelangelo Fiorentino, Rodolfo Montironi, and et al. 2020. "Is There a Role for Immunotherapy in Prostate Cancer?" Cells 9, no. 9: 2051. https://doi.org/10.3390/cells9092051