Table 3.
Main immune checkpoint blockade agents for the treatment of metastatic colorectal cancer
| Intervention | Key trial (NCT number) | Design (N) | Subject | Main results |
|---|---|---|---|---|
| Nivolumab | CheckMate 142 (NCT02060188) | Phase II (N = 74) | MSI-H/dMMR mCRC |
PFS rate: 50% (12 m) OS rate: 73% (12 m) ORR: 31.1% Grade ≥ 3 TRAEs: 21% |
| Nivolumab + ipilimumab | CheckMate 142 (NCT02060188) | Phase II (N = 119) | MSI-H/dMMR mCRC |
PFS rate: 71% (12 m) OS rate: 85% (12 m) ORR: 55% Grade ≥ 3 TRAEs: 32% |
| Nivolumab + ipilimumab | CheckMate 142 (NCT04008030) | Phase II (N = 45) | MSI-H/dMMR mCRC |
PFS rate: 76.4% (12 m) OS rate: 84.1% (12 m) ORR: 69% Grade ≥ 3 TRAEs: 22% |
| Pembrolizumab |
KEYNOTE-164 |
Phase II (N = 124, 61 in cohort A and 63 in cohort B) | MSI-H/dMMR mCRC |
PFS: 2.3 m in cohort A and 4.1 m in cohort B OS: 31.4 m in cohort A and not reached in cohort B ORR: 33% in cohort A and 33% in cohort B Grade ≥ 3 TRAEs: 16% in cohort A and 13% in cohort B |
| Pembrolizumab | KEYNOTE-177 (NCT02563002) | Phase III (N = 307) | MSI-H/dMMR mCRC |
PFS: 8.2 m with chemotherapy and 16.5 m with pembrolizumab treatment Estimated restricted mean survival: 10.8 m with chemotherapy and 13.7 m with pembrolizumab treatment ORR: 33.1% with chemotherapy and 43.8% with pembrolizumab treatment Grade ≥ 3 TRAEs: 66% with chemotherapy and 22% with pembrolizumab treatment |
| Pembrolizumab + lenvatinib |
LEAP-005 |
Phase II (N = 32) | Non-MSI-H/pMMR mCRC |
Median PFS: 2.3 m Median OS: 7.5 m ORR: 22% Grade ≥ 3 TRAEs: 50% |
| Nivolumab + FLOX |
METIMMOX |
Phase II (N = 54) | MSS mCRC |
PFS: 5.6 m with FLOX alone and 6.6 m with repeat sequential FLOX and nivolumab Complete response: 0% with FLOX alone and 16% with repeat sequential FLOX and nivolumab Ongoing objective response: 23% with FLOX alone and 32% with repeat sequential FLOX and nivolumab |
| Nivolumab + regorafenib | NCT04126733 | Phase II (N = 70) | MSS/pMMR CRC |
Median PFS: 15 w in patients without LM and 8 w in patients with LM Median OS: 52 w in patients without LM and 47 w in patients with LM ORR: 21.7% in patients without LM and 0% in patients with LM Grade 3–4 TRAEs: 63% |
mCRC metastatic colorectal cancer, PFS Progression-free survival, OS Overall survival, ORR Objective response rate, TRAEs Treatment-related adverse events, m months, w weeks