Skip to main content

Advertisement

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   28 Nivolumab + local-regional treatment PD-1 + LR ORR: 50%; SD: 21%; mOS: 13.6 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 6 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% 2017 ASCO; [119]
JapicCTI-153098 Biliary tract cancer Ph-1 30 Nivolumab 240 mg, 2-week intervals + cisplatin-gemcitabine PD-1 + Chemo ORR: 36.7%; mPFS: 4.2 months; mOS: 15.4 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:5.9 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 75 mg + durvalumab 1500 mg for 4 doses followed by monthly durvalumab 1500 mg monotherapy PD-L1 + CTLA-4 ORR: HCC, 20%; BTC, 0%; DCR: HCC, 60%; BTC, 41.7%; mPFS: HCC, 7.8 months, nivo alone, 3.1 months; mOS: HCC, 15.9 months; BTC, 5.45 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: 3.4 months; OS rate at 6 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]