The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer
Abstract
:1. Introduction
2. Immune Checkpoint Inhibitors + Chemotherapy
3. Immune Checkpoint Inhibitors + VEGF/EGFR Inhibitors +/− Chemotherapy
4. Immune Checkpoint Inhibitors + Radiotherapy
5. Immune Checkpoint Inhibitors + MEK Inhibitors
6. Novel Combination Therapies
6.1. CSF1R Inhibitors
6.2. IDO1 Inhibitors
6.3. Autologous Tumor Vaccines and Oncolytic Viral Therapy
6.4. T-Cell Bispecific Antibodies
6.5. CD73 Inhibitors
6.6. Gut Microbiota
6.7. Poly-ICLC
6.8. Additional Investigative Agents
7. Conclusions
Funding
Conflicts of Interest
References
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Combination Treatment | ICI | Study Population | Trial ID | Phase | Status |
---|---|---|---|---|---|
Trifluridine + Tipiracil Hychloride | Nivolumab | Refractory, Metastatic MSS CRC | NCT02860546 | II | Completed |
Romidepsin +/− 5-Azacitidine | Pembrolizumab | Refractory, Metastatic MSS CRC | NCT02512172 | I | Recruiting |
Pemetrexed +/− Oxaliplatin | Pembrolizumab | Refractory, Metastatic MSS CRC | NCT03626922 | I | Not yet Recruiting |
Nordic FLOX Regimen | Nivolumab | Untreated, Metastatic MSS CRC | NCT03388190 | II | Recruiting |
Azacitidine | Durvalumab | Refractory, Metastatic MSS CRC | NCT02811497 | II | Recruiting |
Guadecitabine | Nivolumab | Refractory, Metastatic MSS CRC | NCT03576963 | Ib/II | Not yet Recruiting |
FOLFOX | Tremelimumab + Durvalumab | First-line, KRAS-mt CRC | NCT03202758 | Ib/II | Recruiting |
TATE | Nivolumab or Pembrolizumab | Metastatic CRC to liver | NCT03259867 | II | Recruiting |
Combination Regimen | ICI | Study Population | Trial ID | Phase | Status |
---|---|---|---|---|---|
Capecitabine + Bevacizumab | Atezolizumab | Refractory, Metastatic CRC | NCT02873195 | II | Not Recruiting |
SOC Chemotherapy + Bevacizumab | Nivolumab | Metastatic CRC; No Prior Chemotherapy | NCT03414983 | II/III | Recruiting |
Trifluridine/Tipiracil + Oxaliplatin +/− bevacizumab | Nivolumab | Refractory, Metastatic CRC | NCT02848443 | I | Recruiting |
Regorafenib | PDR001 | Refractory, Metastatic MSS CRC | NCT03081494 | I | Recruiting |
Capecitabine + Bevacizumab | Pembrolizumab | Refractory, MSS CRC | NCT03396926 | II | Recruiting |
Cetuximab + Irinotecan | Avelumab | Refractory, BRAF V600E-WT, MSS CRC | NCT03608046 | II | Not yet Recruiting |
Bevacizumab + mFOLFOX6 | PDR001 | Treatment naïve, MSS CRC | NCT03176264 | Ib | Completed |
Panitumumab | Nivolumab + Ipilimumab | Refractory, KRAS/NRAS/BRAF-WT, MSS CRC | NCT03442569 | II | Recruiting |
Radiation Regimen | ICI | Study Population | Study ID | Phase | Status |
---|---|---|---|---|---|
Standard Radiation Therapy | Nivolumab+ Ipilimumab | MSS and MSI-H CRC | NCT03104439 | II | Recruiting |
Hypofractionated palliative radiation | Durvalumab and Tremelimumab | Metastatic MSS CRC | NCT03007407 | II | Recruiting |
Chemo-radiation | Durvalumab | Stage II-IV, MSS Rectal Cancer | NCT03102047 | II | Recruiting |
SBRT to Liver | Pembrolizumab | Metastatic CRC to Liver | NCT02837263 | I | Recruiting |
Radioembolization | Durvalumab and Tremelimumab | Metastatic MSS CRC to Liver | NCT03005002 | I | Active, not recruiting |
High or low-dose radiation therapy | Durvalumab and Tremelimumab | Refractory Metastatic MSS CRC to Liver | NCT02888743 | II | Recruiting |
Combination Regimen | ICI | Study Population | Study ID | Phase | Status |
---|---|---|---|---|---|
Trametinib | Nivolumab +/− Ipilimumab | RAS-mt; previously treated, metastatic MSS CRC | NCT03377361 | I/II | Recruiting |
Binimetinib | Nivolumab +/− Ipilimumab | RAS-mt; previously treated, metastatic MSS CRC | NCT03271047 | I/II | Not Recruiting |
Dabrafenib + Trametinib | PDR001 | BRAFV600E-mt; metastatic CRC | NCT03668431 | II | Recruiting |
Trametinib | Durvalumab | Refractory, metastatic MSS CRC | NCT03428126 | II | By Invitation |
Novel Agents | Therapeutic Targets | ICI | Study ID |
---|---|---|---|
Navarixin | CXCR2 | Pembrolizumab | NCT03473925 |
Olaptesed Pegol | CXCL12 | Pembrolizumab | NCT03168139 |
eFT508 | MNK 1/2 | Avelumab | NCT03258398 |
Ibrutinib | BTK | Pembrolizumab | NCT03332498 |
XL888 | HSP | Pembrolizumab | NCT03095781 |
CGX1321 | PORCN | Pembrolizumab | NCT02675946 |
BBI608 | STAT3/WNT | Pembrolizumab | NCT02851004 NCT03647839 |
Vicriviroc | CCR5 | Pembrolizumab | NCT03631407, NCT03274804 |
Grapiprant | EP4 | Pembrolizumab | NCT03658772 |
Relatlimab | LAG-3 | Nivolumab | NCT03642067 |
Copanlisib | PI3K | Nivolumab | NCT03711058 |
MK-8353 | ERK1/2 | Pembrolizumab | NCT02972034 |
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Hermel, D.J.; Sigal, D. The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer. J. Pers. Med. 2019, 9, 5. https://doi.org/10.3390/jpm9010005
Hermel DJ, Sigal D. The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer. Journal of Personalized Medicine. 2019; 9(1):5. https://doi.org/10.3390/jpm9010005
Chicago/Turabian StyleHermel, David J., and Darren Sigal. 2019. "The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer" Journal of Personalized Medicine 9, no. 1: 5. https://doi.org/10.3390/jpm9010005