Review
Copyright ©The Author(s) 2022.
World J Gastroenterol. Jul 21, 2022; 28(27): 3297-3313
Published online Jul 21, 2022. doi: 10.3748/wjg.v28.i27.3297
Table 1 Complete immune checkpoint inhibitor-based clinical trials in pancreatic ductal adenocarcinoma
Strategy
Treatment
Phase
Number
Cancer stage
Outcomes
Immune checkpoint inhibitor (target) monotherapyTremelimumab (CTLA-4)IINCT02527434Advanced/metastatic PDACTremelimumab monotherapy is ineffective for metastatic PDAC.
Ipilimumab (CTLA-4)IINCT00112580Advanced PDACIpilimumab monotherapy is ineffective for advanced PDAC.
Atezolizumab (PD-L1)I/IINCT03829501Advanced PDACNo results reported yet
Immune checkpoint inhibitor (target) + immune checkpoint inhibitor(target)Tremelimumab (CTLA-4) + Durvalumab (PD-L1)IINCT02558894Metastatic PDACORR 3.1% for combination therapy. (ORR 0% for monotherapy).
Nivolumab (PD-1) + Ipilimumab (CTLA-4)I/IINCT01928394Advanced/metastatic PDACNo results reported yet
Immune checkpoint inhibitor (target) + chemotherapyTremelimumab (CTLA-4) + GemcitabineINCT00556023Advanced PDACMedian OS 7.4 mo (95%CI: 5.8-9.4 mo)
Ipilimumab(CTLA-4) + GemcitabineIbNCT01473940Advanced/metastatic PDACMedian OS 6.90 mo (95%CI: 2.63–9.57 mo)
Pembrolizumab (PD-1) + Gemcitabine and Nab-paclitaxelIb/IINCT02331251Advanced/metastatic PDACMedian OS 15.0 mo (95%CI: 6.8–22.6 mo)
Immune Checkpoint Inhibitor (Target) + Target therapyDurvalumab (PD-L1) + GalunisertibINCT02734160Metastatic PDACMedian PFS 1.9 mo (95%CI: 1.5-2.2 mo); median OS was NR (95%CI: 3.6 mo, NR)
Durvalumab (PD-L1) + PexidartinibINCT02777710Advanced/metastatic PDACNo results reported yet
Immune Checkpoint Inhibitor (Target) + Radiation TherapyTremelimumab (CTLA-4) + Durvalumab (PD-1) + SBRTI/IINCT02311361Advanced/metastatic PDACORR of 9.6% including 2 patients who achieved a durable partial response lasting over 12 mo
https://clinicaltrials.gov/. PDAC: Pancreatic ductal adenocarcinoma; CTLA-4: Cytotoxic T lymphocyte-associated antigen-4; PD-1: Programmed cell death protein 1; PD-L1: Programmed cell death ligand 1; OS: Overall survival; PFS: Progression-free survival; ORR: Overall response rate; NR: Not reached.
Table 2 Complete vaccine immunotherapy-based clinical trials in pancreatic ductal adenocarcinoma
Treatment
Phase
Number
Cancer stage
Outcomes
GVAX, 5-FU, chemoradiationIINCT00084383Resected stage I/II PDAC Median OS 24.8 mo (95%CI: 21.2-31.6 mo)
GVAX, cyclophosphamide, CRS-207IINCT01417000Metastatic PDACCy/GVAX and CRS-207 extended OS for PDAC patients, with minimal toxicity
GVAX, cyclophosphamide, CRS-207IINCT02004262Metastatic PDACCy/GVAX and CRS-207 did not show survival benefit over chemotherapy in patients with previously treated metastatic PDAC
GVAX, Ipilimumab, FOLFIRINOXIINCT01896869Metastatic PDACIpilimumab + GVAX group did not show survival benefit over chemotherapy [median OS 9.38 mo (95% CI, 5.0-12.2 mo) vs 14.7 mo (95%CI: 11.6-20.0 mo)]
Algenpantucel-LIINCT00569387Surgically resected PDACThe addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival (12-mo DFS 62%, 12-mo OS 86%)
Gemcitabine, 5FU Chemoradiation, Algenpantucel-LIIINCT01072981Surgically Resected PDACNo results reported yet
Dendritic cells pulsed with MUC-1/WT-1I/IINCT03114631PDACDendritic cells immunotherapy provided a favorable outcome in PDAC patents (12-mo OS 78.2% vs 33.8%)
GI-4000 (KRAS), GemcitabineIINCT00300950Non-metastatic, Post-resection PDACOverall, GI-4000 group showed a similar pattern of recurrence-free survival and OS compared with the placebo group. For stratified R1 resection subgroup, there was a trend in 1 year OS (72% vs 56%), an improvement in OS (523.5 vs 443.5 d (hazard ratio: 1.06; 95%CI: 0.53–2.13, P = 0.872), and increased frequency of immune responders (40% vs 8%; P = 0.062) for GI-4000 vs placebo.
Ras-peptide vaccine, IL-2, GM-CSFIINCT00019331Metastatic PDACNo results reported yet
GV1001 (telomerase peptide vaccine), Gemcitabine, CapecitabineIIINCT00425360Locally Advanced or Metastatic PDACAdding GV1001 vaccination to chemotherapy did not improve OS.
https://clinicaltrials.gov/. PDAC: Pancreatic ductal adenocarcinoma; Cy: cyclophosphamide; DFS: Disease-free survival; OS: Overall survival.
Table 3 Complete adoptive cell transfer-based clinical trials in pancreatic ductal adenocarcinoma
Treatment
Phase
Number
Cancer stage
Outcomes
MORAb-009, Gemcitabine IINCT00570713Advanced PDAC MORAb-009 did not show survival benefit over placebo group [median OS 6.5 mo, 95%CI: 4.5–8.10 mo vs 6.9 mo 95%CI: 5.4–8.8 mo]
MORAb-009INCT00325494PDACNo results reported yet
Radiolabeled Amatuximab (MORAb-009) INCT01521325PDACNo results reported yet
Autologous Redirected RNA Mesothelin CAR T cellsINCT01897415PDACNo results reported yet
CART-133 T cellsI/IINCT02541370Relapsed and/or Chemotherapy Refractory Advanced PDACNo results reported yet
https://clinicaltrials.gov/. PDAC: Pancreatic ductal adenocarcinoma; OS: Overall survival.
Table 4 Ongoing clinical trials with immunotherapy plus agents targeting the tumor microenvironment in pancreatic ductal adenocarcinoma
Strategy
Treatment
Phase
Number
Cancer stage
Immune checkpoint inhibitor (target) + CAFs/CXCL12 targeted agentsPembrolizumab(PD-1) + Olaptesed pegolI/IINCT03168139Metastatic PDAC
Immune checkpoint inhibitor (target)+ CSF1R targeted agentDurvalumab (PD-L1) + PexidartinibINCT02777710Metastatic/Advanced PDAC
Nivolumab (PD-1) + CabiralizumabINCT02526017Advanced PDAC
Nivolumab (PD-1) + Cabiralizumab + GemcitabineIINCT03697564Advanced PDAC (Stage IV)
Immune checkpoint inhibitor (target) + FAK targeted agentPembrolizumab(PD-1) + DefactinibI/IIaNCT02758587Advanced PDAC
Pembrolizumab(PD-1) + Defactinib + GemcitabineINCT02546531Advanced PDAC
Pembrolizumab (PD-1) + DefactinibIINCT03727880Resectable PDAC
https://clinicaltrials.gov/. PDAC: Pancreatic ductal adenocarcinoma; CTLA-4: Cytotoxic T lymphocyte-associated antigen-4; PD-1: Programmed cell death protein 1; PD-L1: Programmed cell death ligand 1; CAFs: Cancer-associated fibroblasts; CXCL12: CXC motif chemokine ligand 12; CSF1R: Colony-stimulating factor 1 receptor; FAK: Focal adhesion kinase.