Review
Copyright ©The Author(s) 2021.
World J Gastroenterol. Oct 28, 2021; 27(40): 6775-6793
Published online Oct 28, 2021. doi: 10.3748/wjg.v27.i40.6775
Table 1 Clinical trials on pancreatic ductal adenocarcinoma using immunotherapy
National clinical trial number
Sample
Phase
Settings
Drug
Results
NCT0011258082IIAdvanced; Metastatic; Any lineIpilimumabNo improvement in survival rate
NCT0252743464IIAdvanced; Metastatic; ≥ Second lineTremelimumabOS 4 m (95%CI: 2.83-5.42)
NCT0255889465IIMetastatic; ≥ Second lineTremelimumab + Durvalumab vs Durvalumab aloneOS 3.1 m (95%CI: 2.2-6.1) Combination therapy; OS 3.6 m (95%CI: 2.7-6.1) Durvalumab alone
NCT0011258027IIAdvanced; Metastatic; ≥ Second lineIpilimumabNo improvement in survival rate
NCT0337925914IAdvanced (PDAC and other tumors); ≥ Second lineAnti-PD-L1 (BMS-936559)No improvement in survival rate
NCT019283941131I/IIAdvanced (PDAC and other tumors) Any lineNivolumab ± IpilimumabOngoing
NCT03829501412I/IIAdvanced (PDAC and other tumors); ≥ Second lineAtezolizumabOngoing
NCT0308097410IAdvanced (stage III) Any lineNivolumab +Irreversible electroporationPFS 6.3 m (95%CI: 3.5-10.0); OS 18 m (95%CI: 9.2-26.8)
Table 2 Clinical trials on pancreatic ductal adenocarcinoma combining immunotherapy and chemotherapy
National clinical trial number
Sample
Phase
Settings
Drug
Results
NCT0147394021IAdvanced; Metastatic; Any lineIpilimumab; GemcitabineOS 8,5 m (95%CI: 2.2-10.3)
NCT0055602334IMetastatic Chemotherapy naïveTremelimumab GemcitabineOS 7.4 m (95%CI: 5.8-9.4)
NCT0233125181I/IIMetastatic (PDAC and other tumors) Chemotherapy naïvePembrolizumab; Nab-Paclitaxel GemcitabineOS 15 m (95%CI: 6.8-22.6)
Beatty et al, Clin Cancer Res 2013; 19: 6286–629522IAdvanced; First line CD40 agonist (CP-870893); GemcitabinePFS 5.2 m (95%CI: 1.9-7.4); OS 8.4 m (95%CI: 5.3-11.8); 1-y OS 28.6%
NCT0141302247IBorderline; Locally advanced Chemotherapy naïveCCR2 inhibitor (PF-04136309); FOLFIRINOX Combination arm: 49% OR Chemotherapy arm: 0% OR
NCT0226882539IAdvanced; Metastatic (gastrointestinal malignancies) ; Any linePembrolizumab mFOLFOXNo results posted
NCT02309177138IAdvanced; Metastatic (PDAC and other tumors); Any treatment naive Nivolumab; Nab-Paclitaxel GemcitabineNo results posted
NCT0207788198I/IIMetastatic; First lineIDO inhibitor (indoximod); Nab-Paclitaxel; GemcitabineNo results posted
NCT0404573017I/IIMetastatic First lineGemcitabine; Nab-Pacliatxel; PembrolizumabPFS 9.1 m (95%CI: 4.9-13.3); OS 15 m (95%CI: 6.8-23)
NCT0321425030IMetastatic; First lineGemcitabine; Nab-Paclitaxel; Nivolumab; CD40 (agonistic monoclonal antibody) APX005M (sotigalimab)Ongoing
NCT0282648680IIMetastatic; Any lineBL-8040; Pembrolizumab; Pegylated liposomal Irinotecan + 5FUDisease Control Rate 34.5%; OS: 3.3 m Patients receiving study drugs as second-line therapy: 7.5 m
Table 3 Clinical trials on pancreatic ductal adenocarcinoma using vaccines
National clinical trial number
Sample
Phase
Settings
Drug
Results
UMIN00000491931I/IIMetastatic ≥ Second lineKIF20A-66KIF20A-66 vaccine: OS 4.7 m ± 0.8; Best supportive care: OS 2.7 m ± 1.1
UMIN0000009056IAdvanced (gastrointestinal and endocrine malignancies) ; Any lineSVN-2B; IFA; INFa> 50% of the patients had positive clinical and immunological responses
NCT0056938773IIAdjuvant treatmentAlgenpantucel-L12-m OS: 86%
Kaufman et al, J Transl Med 2007; 5: 6010IAdvanced; Metastatic; Any lineMUC1; HLA-A2; ICAM-1; LFA-3; CM-CSFantiCEA/MUC-1 positive: OS 15.1 m; antiCEA/MUC-1 negative: OS 3.9 m
Lepisto et al, Cancer Ther 2008; 6: 955–96412I/IIAdjuvant treatmentMUC1 peptide-loaded DC vaccine Four of twelve patients are still alive without disease recurrence
NCT0141096812IAdvanced; Metastatic; Any linew/Poly-ICLC peptide-pulsed DC-CIKOS 7.7 m
Gjertsen et al, Int J Cancer 2001; 92: 441–5048I/IISurgically resected; Advanced; Any lineK-Ras vaccine GM-CSFResected: OS 25.6 m (95%CI: 10-39); Unresectable: OS 10.2 m (95%CI: 3-28)
Abou-Alfa et al, Am J Clin Oncol 2011; 34: 321–524IAdjuvant (KRAS mutant) Ras-peptide GM-CSFOS 20.3 (95%CI: 11.6-45.3)
Bernhardt et al, Br J Cancer 2006; 95: 1474–148248I/IIAdvanced Treatment naive GV1001; GM-CSFResponders: OS 7.2 m (95%CI: 4.8-10.7); Non-responders: OS 2.9 m (95%CI: 1.7-6.30)
Shima et al, Cancer Sci 2019; 110: 2378-238583IIUnresectable ≥ Second lineSurvivin 2B peptide (SVN-2B); Interferon-βSVN-2B + IFNβ: OS 312 d (95%CI: 43-460); IFNβ: OS 39 d (95%CI: 13-153)
Table 4 Clinical trials on pancreatic ductal adenocarcinoma combining vaccines and chemotherapy
National clinical trial number
Sample
Phase
Settings
Drug
Results
Jaffee et al, J Clin Oncol 2001; 19: 145–5614IAdjuvant (stage I/II/III) CVAX, ChemorradiationEffective anti-tumor immunty
NCT0008438360IIAdjuvant (stage I/II) GVAX; 5FU; ChemorradiationCombination: OS 24.8 m (95%CI: 21.2-31.6); 5FU/Chemorradiation: OS 20.3 m (95%CI: 18-23.9)
NCT0141700093IIaMetastatic ≥ Second lineGVAX/Cy CRS-207Combination: OS 6.28 m (95%CI: 4.47-9.40); GVAX/Cy: OS 4.07 m (95%CI: 3.32-5.42)
NCT02004262303IIbMetastatic ≥ Second lineGVAX/Cy CRS-207 ChemotherapyCombination: OS 3.7 m (95%CI: 2.9-5.3); CRS-207 alone: OS 5.4 m (95%CI: 4.2-6.4); Chemotherapy: OS 4.6 m (95%CI: 4.2-5.7)
UMIN00000808260IIAdvanced First lineKIF20A; VEGFR1/2; GemcitabineOS 9 m HLA matched; OS 10 m HLA unmatched
NCT01072981722IIIAdjuvant treatment Algenpantucel-L; Gemcitabine-5FU1-y DFS 86% algenpantucel-L vs 63% Gemcitabine-5FU; 1-y OS 65% algenpantucel-L vs 45% Gencitabine-5FU
NCT01836432302IIIBorderline resectable; Locally advanced usresectable; First lineAlgenpantucel-L; FOLFIRINOX; Gemcitabine; Nab-Paclitaxel; Capecitabine; 5FUNo results posted
NCT0178152047I/IIUnresectable locally advancedMetastatic Chemotherapy naïve DC-CIK Chemotherapy S-1DC-CIK+Chemotherapy S-1: OS 7 m; DC-CIK alone: OS 4.2 m; Chemotherapy S-1 alone: OS 4.7 m; Supportive care only: OS 1.73 m
Muscarella et al, J Clin Oncol 2012; 30: e14501-e.176IIResected (KRAS mutant) adjuvantGI-4000 GemcitabineGI-4000+Gemcitabine OS 19.8 m; Placebo-gemcitabine: OS 14.8 m
Middleton et al, Lancet Oncol 2014; 15: 829–8401062IIIAdvancedMetastatic Chemotherapy naïveGV1001 Gemcitabine CapecitabineTreated group: OS 6.9 m (95%CI: 6.4-7.6); Chemotherapy alone: OS 7.9 m (95% 7.1-8.8)
Yanagisawa et al, Anticancer Res 2018; 38: 2217-22258IAdjuvant (I, II, III) WT1-DC VaccineS-1 Chemotherapy GemcitabineNo results posted
Suzuki et al, Cancer Sci 2017; 108: 73-8066IIAdvanced First lineAntiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide; GemcitabinePFS HLA matched: 4.7 m; PFS HLA unmatched: 5.2 m
Table 5 Clinical trials on pancreatic ductal adenocarcinoma combining vaccines and immunotherapy
National clinical trial number
Sample
Phase
Settings
Drug
Results
NCT0083640730IMetastatic ≥ Second lineIpilimumab GVAXCombination: OS 5.7 m (95%CI: 4.3-14.7); Ipilimumab: OS 3.6 m (95%CI: 2.5-9.2)
NCT0224337193IIMetastatic ≥ Second lineNivolumab Cy; GVAX; CRS-207No results posted
NCT0245198262I/IINeoadjuvant Adjuvant Nivolumab Cy GVAX UrelumabNo results posted
NCT046272463I/IIAdjuvant DC vaccine loaded with personalized peptides (PEP-DC); Nivolumab SOCNo results posted
NCT0243296311IAdvanced (solid malignancies) ≥ Second linePembrolizumab p53MVAClinical responses in three out of eleven patients
Table 6 Clinical trials on pancreatic ductal adenocarcinoma using adoptive cell transfer
National clinical trial number
Sample
Phase
Settings
Drug
Results
NCT00570713155IIUnresectable First-lineMORb-009 GemcitabineCombination: OS 6.5 m (95%CI: 4.5-8.10); Placebo plus Gemcitabine: OS 6.9 m (95%CI: 5.4-8.8)
NCT0193584310I/IIAdvanced (PDAC and other tumors Her2-positive) ≥ Second lineHer2-specific CAR-T cells OS 4.8 m (95%CI: 1.5-8.3)
NCT0178152047I/IIAdvanced; Any lineDC-CIK Chemoterapy S-1DC-CIK + Chemotherapy S-1: OS 7 m DC-CIK alone: OS 4.2 m; Chemotherapy S-1 alone: OS 4.7 m; Supportive care only: OS 1.73 m
Aoki et al, Cytotherapy 2017; 19: 473-48548IAdjuvant Gemcitabine; Autologous γδ; T-cell transferPFS 26 m (no statistical diference); OS No statistical difference
NCT0195967211I/IINeoadjuvant Gemcitabine; Leucovorin-Fluorouracil; Oregovomab; Nelfinavir + SBRTPrematurely closed; PFS 8.6 m; OS 13 m (95%CI: 7-22)
NCT0072078540IMetastatic (PDAC and other tumors) ≥ Second lineIrreversible electroporation (IRE); Allogeneic natural killer cell therapyNo results posted
NCT0421202667IMetastatic ≥ Second lineIrreversible electroporation; Allogeneic natural killer cell therapyStage III PFS 9,1 m (IRE-NK) vs 7.9 m (IRE); Stage III OS 13.6 m (IRE-NK) vs 12.2 m (IRE); Stage IV OS 10.2 m (IRE-NK) vs 9.1 m (IRE)
NCT015836866IMetastatic ≥ Second lineMesothelin-CART2 patients stabilized diseasePFS patient 1: 3.8 mPFS patient 2: 5.4 m