Key clinical trials of ICI-based immunotherapy in MSI-H/dMMR and/or MSS/pMMR CRC cohorts
| Trial | Treatment regimen | Target population | Number of patients | Sponsor | Outcomes |
|---|---|---|---|---|---|
| Targeting MSI-H/dMMR CRCs | |||||
| KEYNOTE-016 | Pembrolizumab in chemorefractory patients | MSI-H/dMMR CRC; MSS/pMMR CRC | 9 (MSI-H)/41 | Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins | ORR of MSI-H CRC 40.0% |
| KEYNOTE-164 | Pembrolizumab in chemorefractory patients | MSI-H/dMMR mCRC with ≥ 1 prior line of therapy | 63 | Merck Sharp & Dohme LLC | ORR 33%, mPFS 4.1 months |
| CheckMate-142 | Nivolumab plus ipilimumab | MSI-H/dMMR mCRC with no prior treatment | 45 | Bristol-Myers Squibb | ORR 69%, DCR 84% |
| KEYNOTE-177 | Pembrolizumab as first-line therapy | MSI-H/dMMR CRC | 307 | Merck Sharp & Dohme LLC | ORR 45.1%, mPFS 16.5 months |
| NICHE | Ipilimumab plus nivolumab; pMMR group with or without celecoxib | MSI-H/dMMR or MSS/pMMR CRC | 40 | The Netherlands Cancer Institute | ORR 100% in dMMR CRC, 27% in pMMR CRC |
| Targeting MSS/pMMR CRCs | |||||
| REGONIVO | Regorafenib plus nivolumab | MSS/pMMR CRC with ≥ 2 previous lines of chemotherapy | 25 | Kohei Shitara, National Cancer Center Hospital East | ORR 36%, mPFS 7.9 months |
| REGOTORI | Regorafenib plus toripalimab | MSS/pMMR CRC with ≥ 2 previous lines of chemotherapy | 42 | Second Affiliated Hospital, School of Medicine, Zhejiang University | ORR 15.2%, mPFS 2.1 months, mOS 15.5 months |
| Fakih 2023 | Regorafenib, ipilimumab and nivolumab | MSS/pMMR mCRC | 39 | City of Hope Medical Center | ORR 27.6%, mPFS 4 months, mOS 20 months |
| KEYNOTE-651 | mFOLFOX7 plus pembrolizumab | MSS/pMMR mCRC with no prior treatment | 31 | Merck Sharp & Dohme LLC | mPFS 9 months, mOS 29 months |
| METIMMOX-2 | Oxaliplatin plus nivolumab | MSS/pMMR mCRC with no prior treatment | 28 | University Hospital, Akershus | ORR 32% |
| BBCAPX | Sintilimab plus bevacizumab and oxaliplatin and capecitabine | RAS-mutant and MSS/pMMR mCRC with no prior treatment | 25 | Second Affiliated Hospital, School of Medicine, Zhejiang University | ORR 84.0%, DCR 100%, mPFS 18.2 months |
| NIVACOR | FOLFOXIRI plus bevacizumab and nivolumab | RAS/BRAF-mutant mCRC | 52 (MSS)/73 | Gruppo Oncologico Italiano di Ricerca Clinica | MSS CRC: ORR 78.9%, DCR 96.2%, mPFS 9.8 months |
DCR, disease control rate; mPFS, median progression-free survival; mOS, median overall survival; ORR, objective response rate.