Table 2.
Clinical trials on MSS CRCs
| Identifier | Phase | Setting | Treatment | Participants | Outcome measures | Completion date |
|---|---|---|---|---|---|---|
| NCT02693535 | 2 | Advanced solid sumors | Many, incl. pembrolizumab, ipilimumab + nivolumab | 660 | ORR | Dec 2021 |
| NCT03519412 | 2 | pMMR CRCs | Temazolamide (priming), pembrolizumab | 348 | ORR, PFS, OS | June 2022 |
| NCT04014530 | 1/2 | Metastatic pMMR and dMMR colorectal adenocarcinomas or metastatic dMMR endometrial carcinoma | Pembrolizumab + ataluren | 47 | ORR, PFS, OS | Aug 2023 |
| NCT03435107 | 2 | dMMR or POLE mutated mCRCs | Durvalumab | 33 | Objective response rates (RECIST 1.1) | May 2022 |
| NCT03827044 | 3 | MSI-H or POLE Exonuclease Domain mutant colon cancer | Avelumab plus 5-FU based chemotherapy | 402 | DFS, OS | July 2028 |
| NCT03104439 | 1 | MSI-H and MSS CRCs, pancreatic cancer | Nivolumab + ipilimumab + radiation therapy | 80 | PFS, OS | Oct 2024 |
| NCT03832621 | 2 | mCRCs | Temozolomide + nivolumab + ipilimumab | 100 | PFS, ORR, DOR | Feb 2022 |
| NCT03935893 | 2 | Advanced solid cancers | TIL, fludarabine + cyclophosphamide combination | 10 | ORR, CRR, DOR, DCR, PFS, OS | June 2030 |
| NCT03555149 | 1/2 | mCRCs excluding MSI-H | Atezolizumab + imprime PGG + bevacizumab, atezolizumab + isatuximab, atezolizumab + selicrelumab + bevacizumab, atezolizumab + idasanutlin, atezolizumab + regorafenib, atezolizumab + regorafenib + AB928 | 326 | ORR, DOR, DCR, PFS, OS | Jan 2022 |
| NCT03373188 | 1 | Resectable rancreatic and colorectal cancer | Anti-SEMA4D + surgery, anti-SEMA4D + ipilimumab or nivolumab + surgery | 32 | CD8+ T cell infiltration, AEs | Dec 2022 |
| NCT03250832 | 1 | Advanced solid tumors | TSR-033 + anti-PD-1 | 200 | AEs, CR, OS, PFS | May 2021 |
| NCT03642067 | 2 | MSS advanced colorectal cancer | Nivolumab + relatlimab | 64 | ORR, drug-related toxicities | Feb 2023 |
| NCT04117087 | 1 | Resected pMMR CRCs | KRAS peptide vaccine + nivolumab + ipilimumab | 30 | DFS, AEs, CD8 and CD4 T cells | June 2024 |
| NCT02851004 | 1/2 | mCRC | BBI608 + pembrolizumab | 94 | ORR, PFS, OS | Oct 2020 |
| NCT03711058 | 1/2 | Relapsed/Refractory solid tumors with expansions in MSS colorectal cancer | Copanlisib and nivolumab | 54 | MTD, ORR, DCR, PFS, OS | Jan 2022 |
| NCT04110093 | 1/2 | CRCs | Regorafenib + anti-PD-1 | 120 | ORR, PFS, OS | Aug 2021 |
| NCT04271813 | 2 | Advanced colorectal cancer | Anlotinib + sintilimab | 30 | PFS, OS | Dec 2021 |
| NCT03207867 | 2 | Solid tumors and non-Hodgkin lymphoma | NIR178 + PDR001 (mAb) | 310 | ORR, OS, PFS, DCR | June 2021 |
| NCT03549000 | 1 | Advanced malignancies | Anti-CD73 NZV930 + NIR178 or PDR001 (mAb) or both | 344 | ORR, PFS, CBR, safety and tolerability | Feb 2022 |
| NCT03150706 | 2 | dMMR or POLE mutated mCRCs | Avelumab | 33 | Serum CEA, TSH, T3, free T4, EKG | Dec 2021 |
| NCT04262687 | 2 | MSS metastatic colorectal cancer with high immune infiltrate | CAPEOX+ bevacizumab + pembrolizumab | 55 | OS, serum CEA and CA199 | Dec 2023 |
| NCT03189030 | 1 | Colorectal neoplasms | personalized live, attenuated, double-deleted Listeria monocytogenes (pLADD)-based immunotherapy | 28 | Safety and Tolerability | Dec 2020 |
| NCT04108481 | 1/2 | mCRCs | Y-90 glass microspheres + durvalumab | 18 | MTD, ORR, DCR, PFS, OS | Oct 2021 |
| NCT04109755 | 2 | Localised MSS rectal cancer | Pembrolizumab + radiotherapy | 25 | TRG, OS, DFS, DMFS | March 2028 |
| NCT03377361 | 1/2 | Previously treated metastatic colorectal cancers | Nivolumab + trametinib +/− ipilimumab | 345 | ORR, PFS, OS, AE | Nov 2022 |
| NCT03102047 | 2 | Stage II-IV rectal cancer | Chemotherapy + radiotherapy, durvalumab, and surgery | 47 | Pathologic response, ORR, AE | Jan 2021 |
| NCT03626922 | 1b | mCRC | Pemetrexed +/− oxaliplatin + pembrolizumab | 33 | Safety/tolerability, RP2D | Nov 2021 |
| NCT02671435 | 1/2 | MSS mCRC (cohort A) | Durvalumab + monalizumab + mFOLFOX +/− bevacizumab +/− cetuximab | 36 | Safety/tolerability, DOR, PFS/OS | Mar 2022 |
| NCT03174405 | 2 | MSS mCRC | FOLFOX + cetuximab + avelumab | 43 | PFS, ORR, safety | Aug 2021 |
| NCT02860546 | 2 | MSS mCRC | TAS-102 + nivolumab | 35 | ORR | Nov 2017 |
| EudraCT 2017-004392-32 | 2 | RAS wild type mCRC | Avelumab + cetuximab | 75 | OS, ORR, PFS, safety | N/A |
| NCT03391232 | 1 | MSS mCRC | PolyPEPI1018 + 5-FU + bevacizumab | 11 | Safety, immune response | July 2019 |
| NCT03256344 | 1b | mCRC | Talimogene laherparepvec + atezolizumab | 36 | Safety, ORR, PFS/OS | May 2022 |
| NCT03539822 | 1 | Advanced GI cancers | Cabozantinib + durvalumab | 30 | RP2D, AE, ORR, DCR, PFS/OS | Dec 2020 |
| NCT02837263 | 1b | MSS mCRC | SBRT + pembrolizumab + surgery | 15 | Recurrence rate, Time to recurrence, DFS, OS | Jun 2021 |
| NCT03657641 | 1/2 | mCRC | Regorafenib + pembrolizumab | 75 | Safety/tolerability, PFS/OS | Jun 2022 |
| NCT03865082 | 2 | MSS mCRC | Tilsotolimod (intratumoral) + nivolumab + ipilimumab | 77 | ORR, safety/tolerability | Apr 2022 |
| NCT03435640 | 1b/2 | MSI-H and MSS mCRC (phase 2 expansion cohort) | NKTR-262 + NKTR-214 + nivolumab | 383 (all cohorts) | Safety/tolerability, ORR | Dec 2022 |
| NCT03168139 | 1/2 | mCRC and pancreatic cancer | Olaptesed (NOX-A12) + pembrolizumab | 20 | Safety/tolerability, DCR | Mar 2020 |
| NCT02260440 | 2 | MSS mCRC | Azacitidine + pembrolizumab | 31 | ORR, PFS, OS, safety | Sept 2017 |
| NCT02512172 | 1 | MSS mCRC | Azacitidine + romidepsin + pembrolizumab | 30 | Safety/tolerability, ORR, immune correlatives | Dec 2020 |
| NCT02437136 | 1b/2 | MSS mCRC (phase 2 expansion cohort) | Entinostat + pembrolizumab | 202 (all cohorts) | Safety/tolerability, ORR, DCR, PFS/OS, DOR, TTR | N/A |
Abbreviations: ORR: Objective response rate; DCR: Disease control rate; DOR: Duration of response; PFS: Progression-free survival; CR: complete response; PR: Partial response; OS: Overall survival; DLTs: dose-limiting toxicities; pCR: pathological complete response; MTD: maximum tolerated dose; TRG: tumor regression grade; DMFS: distant metastasis-free survival; CBR: Clinical Benefit Rate; AE: Adverse Events.