Table 3 Key trials of combination immunotherapy in hepatocellular, biliary tract, and pancreatic 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-040 retrospectively evaluate; | Advanced HCC | Â | 28 | Nivolumab + local-regional treatment | PD-1 + LR | ORR: 50%; SD: 21%; mOS: 13.6Â months | Grade 3: 7% | 2018 ASCO; [116] |
NCT03006926 | Unresectable HCC; | Ph-1b | 13 | Lenvatinib + pembrolizumab | PD-1 + Target | ORR: 46%; SD: 46%; | Any grade: 94%; decreased appetite: 56%; hypertension: 56% | 2018 ASCO; [117] |
NCT02715531 | Unresectable or metastatic HCC | Ph-1b | 68 | Atezolizumab + bevacizumab | PD-L1 + Target | ORR: 34%; PFS rate at 6Â months: 71% | Any grade: 72%; Grade 3/4: 25% | 2018 ESMO; [118] |
Study-022; NCT02519348 | Advanced HCC | Ph-1/2 | 40 | Durvalumab + tremelimumab | PD-L1 + CTLA-4 | ORR: 18%; DCR: 57.5% | Any grade: 72%; Grade 1–3: 20% | |
JapicCTI-153098 | Biliary tract cancer | Ph-1 | 30 | Nivolumab 240Â mg, 2-week intervals + cisplatin-gemcitabine | PD-1 + Chemo | ORR: 36.7%; mPFS: 4.2Â months; mOS: 15.4Â months | Malaise (8/30, 27%) and decreased appetite (7/30, 23%) | 2019 ASCO; [120] |
2018 ASCO Poster | Advanced intrahepatic cholangiocarcinoma | 14 | Lenvatinib + pembrolizumab or nivolumab | PD-1 + Targeted | ORR: 21.4%; DCR: 92.9%; mPFS:5.9Â months | Grade 3: 14% | 2018 ASCO; [121] | |
NCT01938612 | Biliary tract cancer | Ph-1 | 65 | Durvalumab 20 mg/kg + tremelimumab 1.0 mg/kg, q4w; durvalumab monotherapy | PD-L1 + CTLA-4 | DCR: D, 16.7%; D + T, 32.2%; mPFS: D, 9.7 months, D + T, 8.5 months; mOS: D, 8.1 months; D + T, 10.1 months | Any grade: D, 64%; D + T, 82%; Grade ≥ 3: D, 19%; D + T, 23%; D + T: a death due to drug-induced liver injury | 2019 ASCO; [122] |
NCT02821754 | Advanced HCC; advanced BTC | Ph-2 | 22 | Monthly tremelimumab 75Â mg + durvalumab 1500Â mg for 4 doses followed by monthly durvalumab 1500Â mg monotherapy | PD-L1 + CTLA-4 | ORR: HCC, 20%; BTC, 0%; DCR: HCC, 60%; BTC, 41.7%; mPFS: HCC, 7.8Â months, nivo alone, 3.1Â months; mOS: HCC, 15.9Â months; BTC, 5.45Â months | Grade 3/4: lymphocytopenia, hyponatremia, bullous dermatitis, maculopapular rash | 2019 ASCO; [123] |
KEYNOTE-202; NCT02826486 | Metastatic pancreatic adenocarcinoma | Ph-2a | 37 | BL-8040 + pembrolizumab | PD-1 + Molecules | PR: 3.4%; DCR: 34.5%; mOS: 3.4Â months; OS rate at 6Â months: 34.9% | 2018 ESMO; [124] | |
NCT02309177 | Advanced pancreatic cancer | Ph-1 | 50 | Nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2 on day 1, 8, and 15 + nivolumab 3 mg/kg on d 1 and 15 of each 28-day cycle | PD-1 + Chemo | ORR: 18%; DCR:64%; mPFS: 5.5 months; mOS: 9.9 months | Grade 3/4: 96%; Grade 5: 1 pts | 2019 ASCO; [125] |
NCT02311361 | Advanced pancreatic adenocarcinoma | Ph-1/2 | 51 | Cohort 1: Durvalumab + SBRT; Cohort 2: SBRT followed by durvalumab; Cohort 3: Durvalumab + Tremelimumab + SBRT; Cohort 4: SBRT followed by Durvalumab + Tremelimumab | PD-L1 + CTLA-4 + RT; PD-L1 + RT | PR: cohort 1, 1 pt.; cohort 4, 2 pts.; mPFS and mOS: cohort 1, 1.7 months, 3.4 months; cohort 2, 2.6 months, 9.1 months; cohort 3, 1.6 months and 3.0 months; cohort 4, 3.2 months, 6.4 months | The most commonly TRAEs were lymphopenia. Grade 3–4: lymphopenia and anemia | 2019 ASCO; [126] |