Table 1.
Selection of completed trials investigating the use of immune checkpoint inhibitors for proficient mismatch repair (pMMR) or non-specified microsatellite status (MSI n.s.) colorectal cancer.
| Study Nameand/or NTC | Phase | Study Population | Agent(s) | End-Points * | Results |
|---|---|---|---|---|---|
| Anti-VEGF and Chemotherapy + Immune Checkpoint Inhibitors | |||||
| NCT0237335672 [21] | II | 1st line mCRC MSI n.s. |
FOLFOX + Pembrolizumab | 1: PFS 2: ORR, DCR |
mPFS not reached ORR: 53%, DCR: 100% |
| MODUL cohort 2 NCT02291289 [22] | II | 1st line mCRC BRAF wt, MSI n.s. |
FOLFOX + BV followed by FP + BV vs. FP + BV + Atezolizumab | 1: PFS 2: OS |
PFS: 7.4 mos vs. 7.2 mos, HR 0.96, p = 0.727 OS: 51%, HR = 0.86, p = 0.28 |
| BACCI NCT02873195 [23] | II | Pretreated mCRC MSI n.s. |
Capecitabine + BV + Atezolizumab vs. Capecitabine + BV | 1: PFS 2: 12 mo OS |
mPFS: 4.4 mos vs. 3.3 mos. HR 0.72, p = 0.051 12 mo OS: 43% vs. 52%, HR 0.94, p = 0.4. |
| NCT01633970 [24] | Ib | 1st line mCRC MSI n.s. |
FOLFOX + BV + Atezolizumab | 1: Safety 2: PFS, OS |
mPFS: 14.1 mos OR: 52% |
| ATEZOTRIBE NCT03721653 [25] | II | 1st line mCRC MSI n.s. |
FOLFOXIRI + BV + Atezolizumab vs. FOLFOXIRI + BV | 1: PFS 2: ORR, irORR, R0 resection rate |
No results posted |
| Anti-EGFR ± Chemotherapy + Immune Checkpoint Inhibitors | |||||
| AVETUX NCT03174405 [26] | II | 1st line mCRC RAS/BRAF wt MSI n.s. |
FOLFOX + Cetuximab + Avelumab | 1: 12 mos PFS 2: PFS, ORR |
12 mo PFS: 40% mPFS: 11.1 mos ORR: 79.5% |
| CAVE Eudract 2017-004392-32 [27] | II | Pretreated mCRC RAS wt, MSI n.s. |
Cetuximab + Avelumab | 1: OS 2: ORR, PFS, Safety |
No results posted |
| Anti-TAMs + Immune Checkpoint Inhibitors | |||||
| REGONIVO NCT03406871 [28] | Ib | Preatreatd mCRC MSI n.s. |
Regorafenib + Nivolumab | 1: Safety 2: ORR, PFS, OS |
ORR: 36% mPFS: 5.6 mos mOS: not reached |
| NCT03712943 [29] | I/Ib | Preatreatd mCRC pMMR |
Regorafenib + Nivolumab | 1: Safety 2: ORR, PFS, OS |
ORR: 5% mPFS: 4.3 mos mOS: 11 mos |
| REGOMUNE NCT03475953 [30] | II | Pretreated mCRC pMMR |
Regorafenib + Avelumab | 1: ORR 2: PFS, OS |
ORR: 0% mPFS: 3.6 mos mOS: 10.8 mos |
| Radiotherapy + Immune Checkpoint Inhibitors | |||||
| NCT03104439 [31] | II | Preatreatd mCRC pMMR | SBRT 8 Gy + Nivolumab + Ipilimumab | 1: DCR 2: ORR |
DCR: 17.5% ORR: 7.5% |
* Primary end-points (1) and authors’ selected secondary end-points (2) are listed. Abbreviations: BV: Bevacizumab; DCR: Disease Control Rate; EGFR: Epidermal Growth Factor Receptor; FOLFOX: 5-FU + Folinic Acid + Oxaliplatin; FP: Fluoropyrimidine; HR: Hazard Ration; irORR: immune-related Overall Response Rate; mCRC: Metastatic Colorectal Cancer; mos: months; ORR: Overall Response Rate; OS: Overall Survival; PFS: Progression Free Survival; SBRT: Stereotactic Body Radiation Therapy; TAMs: Tumor-Associated Macrophages; VEGF: Vascular Endothelial Growth Factor.