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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 3 mg/kg + ipilimumab 1 mg/kg q3w, followed by nivolumab 3 mg/kg once q2w PD-1 + CTLA-4 ORR: 55%; DCR: 80%; PFS rate at 12 months: 71%; OS rate at 12 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% 2017 ASCO; [135]
NCT01988896 Metastatic colorectal cancer Ph-1b 84 Atezolizumab + cobimetinib PD-L1 + Target ORR: 8%; DCR: 31%; OS rate at 12 months: 43%; mOS: 9.8 months; PFS rate at 6 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 8 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% 2017 ASCO; [137]
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]