Table 4 Key trials of combination immunotherapy in colorectal cancers
From: Combination regimens with PD-1/PD-L1 immune checkpoint inhibitors for gastrointestinal malignancies
Study/trial identifier | Tumor type | Phase | Participants | Combination intervention | Combination regimen type | Clinical endpoints | TRAEs | Reference |
|---|---|---|---|---|---|---|---|---|
CheckMate-142; NCT02060188 | DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer | Ph-2 | 119 | Nivolumab 3Â mg/kg + ipilimumab 1Â mg/kg q3w, followed by nivolumab 3Â mg/kg once q2w | PD-1 + CTLA-4 | ORR: 55%; DCR: 80%; PFS rate at 12Â months: 71%; OS rate at 12Â months: 85% | Grade 3/4: 32% | 2018 JCO; [134] |
NCT01633970 | Metastatic colorectal cancer | Ph-1 | 44 | Arm A, MPDL3280A (anti-PDL1) + bevacizumab; Arm B, MPDL3280A + bevacizumab + FOLFOX | PD-L1 + Target; PD-1 + Target + Chemo | ORR: Arm A, 8%; Arm B, 36%; | Grade 3/4: Arm A, 64%; Arm B, 73% | |
NCT01988896 | Metastatic colorectal cancer | Ph-1b | 84 | Atezolizumab + cobimetinib | PD-L1 + Target | ORR: 8%; DCR: 31%; OS rate at 12Â months: 43%; mOS: 9.8Â months; PFS rate at 6Â months: 18% | Any grade: 96%; Grade 3/4: 32% | 2018 ASCO; [136] |
NCT02375672 | Colorectal cancer irrespective of MMR status | Ph-2 | 40 | Pembrolizumab + mFOLFOX6 | PD-1 + Chemo | ORR: 53%; DCR at 8Â weeks: 100% | Grade 3/4: 36.7% | 2017 ASCO; [135] |
NCT02437071 | Mismatch repair proficient (pMMR) metastatic colorectal cancer | Ph-2 | 26 | Pembrolizumab + radiotherapy; pembrolizumab + ablation | PD-1 + RT; PD-1 + LR | ORR: RT cohort, 9%; LR cohort, no responses | Grade 1/2: 73% | |
NCT02981524 | Mismatch repair–proficient (MMR-p) advanced colorectal cancer | Ph-2 | 17 | Pembrolizumab + CyGVAX colon vaccine + cyclophosphamide | PD-L1 + vaccine + chemo | ORR: 18%; mPFS: 2.7 months; mOS: 7.0 months | Two patients (12%) had grade 3/4 adverse events that were attributed to study therapy | 2019 ASCO; [138] |
NCT02870920 | Advanced refractory colorectal carcinoma, not selected for dMMR | Ph-2 | 180 | Durvalumab 1500 mg D1 q 28 days + tremelimumab 75 mg D1 for first 4 cycles vs BSC | PD-1 + CTLA-4 | DCR: D + T, 22.7%; BSC, 6.6%; mOS: D + T, 6.6 months, BSC, 4.1 months | Grade 3/4: abdominal pain, fatigue, lymphocytosis and eosinophilia were significantly higher in D + T | 2019 ASCO; [139] |