Table 1.
Summary of clinical trials for the indicated immunotherapy approaches
| Immunotherapeutic treatment | ID number | Phase | No. of patients | Cohort composition | Strategy | Results |
|---|---|---|---|---|---|---|
| Whole cell-based vaccination | [18] | I | 14 | Surgically resected | GVAX + chemoradiotherapy | No toxicities; dose-dependent antitumor immunity increased |
| NCT00084383[19] | II | 60 | Surgically resected | GVAX + chemoradiotherapy | Expansion of CD8+ T cells; increased OS | |
| [20] | Pilot study | 50 | ADV | GVAX + cyclophosphamide | Minimal toxicities; increased T cell response; improved OS | |
| NCT00727441[21] | II | 87 | Surgically resectable | GVAX ± cyclophosphamide | TLS formation; increased T cell response; increased OS | |
| NCT00585845[23] | I | 17 | Treatment-refractory | CRS-207 | Dose-dependent antitumor immunity increased | |
| NCT01417000[24] | II | 93 | Pretreated metastatic | GVAX + cyclophosphamide ± CRS-207 | Minimal toxicities; increased T cell response; increased OS | |
| NCT02004262[25] | IIb | 213 | Pretreated metastatic | GVAX + cyclophosphamide + CRS-207; CRS-207 alone; CT | GVAX + CT + CRS-207 no improved survival over CT | |
| Peptide-based vaccination | [27] | I/II | 5 | ADV | Synthetic RAS-loaded APCs | 2/5 pts showed increased immune response and OS |
| CTN-95002/97004[28] | I/II | 48 | 10 resected/38 ADV | Synthetic RAS-loaded APCs + GM-CSF | Increased OS and immune response in 58% of pts | |
| CTN-95002/98010[29] | 10 yrs follow-up | 23 | Surgically resected | Synthetic RAS-loaded APCs + GM-CSF | Long-lasting vaccine-induced immune response in 85% of pts | |
| [31] | I/II | 48 | Unresectable | GV1001 + GM-CSF | Vaccination well tolerated; immune response in 75% of pts | |
| ISCRCTN-4382138[32] | III | 1062 | ADV/Metastatic | CT; GV1001 after or with CT | No differences between CT and combined treatment | |
| UMIN000000905[35] | I | 6 | Unresectable ADV | Survivin-2B80-88 + IFN-α | > 50% of pts with positive clinical and immunological responses | |
| UMIN000012146[36] | II | 83 | HLA-A24+ | Survivin-2B80-88 ± IFN-β | Combined treatment increased pts survival w/o toxicity | |
| Dendritic cell-based vaccination | [41] | I/II | 10 | Surgically resected | MUC1 peptide-loaded DCs | No toxicity; 3/10 pts alive after 4 yrs |
| 06DZ19009[42] | I | 7 | Metastatic | MUC1 peptide-loaded DCs | No toxicity; no clinical benefits | |
| UMIN000004855[44] | I | 10 | HLA-A2*2402 | WT1 peptide-loaded DCs | No toxicity; increased survival only in pts w/o liver metastasis | |
| UMIN000004063[45] | I | 10 | ADV | WT1 peptide-loaded DCs ± GEM | No toxicity; increased OS and PFS in 50% of pts | |
| NCT01410968[47] | I | 12 | Metastatic | hTERT/CEA/Survivin peptide loaded DCs + poly (IC:LC) | Fatigue and/or flu-like symptoms; 4/12 pts SD and 4/12 pts PD | |
| Adoptive cell transfer | NCT00965718[75] | II | 43 | Surgically resected | MUC1-CTLs + GEM | Reduction of liver and local recurrences |
| [77] | 20 | Treatment-refractory | CIK cells ± GEM | No differences observed between CT and combined therapy | ||
| [78] | 58 | Pretreated ADV | CIK cells ± S-1 | No differences observed between CT and combined therapy | ||
| CAR-T | NCT01897415[109] | I | 6 | Treatment-refractory | Anti-MSLN CAR-T | 2 pts with SD; MAV tumor lesions stable in 3 pts and decreased in 1 pt by 69.2% |
| Monoclonal antibody | NCT00711191[154] | I | 22 | CT-naïve ADV | CP-870,893 + GEM | 4 pts PR; 11 pts SD |
| Immune checkpoint inhibitors | NCT00112580[177] | II | 27 | ADV/metastatic | Ipilimumab (anti-CTLA-4) | 1/27 subject showed a significant delayed response |
| NCT00729664[180] | I | 14 | ADV | BMS-936559 (anti-PD-L1) | No response observed | |
| NCT01876511[181] | II | 8 | MMR-deficient | Pembrolizumab (anti PD-1) | 2 CR; 3 PR; 1 SD | |
| NCT00556023[187] | Ib | 34 | ADV | GEM ± Tremelimumab (anti-CTLA-4) | 6% PR; 21% SD; OS 7.4 months | |
| NCT01473940[188] | Ib | 21 | Unresectable ADV | GEM ± Ipilimumab (anti-CTLA-4) | Safe and tolerable regimen; 14% ORR; 33% SD; OS 6.9 months | |
| NCT023311251[189] | Ib/II | 17 | Pretreated/CT naive | Pembrolizumab (anti-PD-1) + GEM/nab-P | 25% PR; 67% SD; OS 15 months (CT naïve pts); no PD pts | |
| NCT02309177[190] | I | 42 | CT-naïve ADV | Nivolumab (anti-PD-1)/nab-P ± GEM | 2% CR; 16% PR; 46% SD; OS 9.9 months | |
| [197] | I | 30 | Pretreated ADV | Ipilimumab (anti-CTLA-4) ± GVAX | OS 5.7 months in pts with combined therapy, compared to 3.6 months in pts treated with ipilimumab alone |
Pts: patients; PD: progressive disease; TLS: tertiary lymphoid structures; Yrs: years; PR: partial response; MAV: metabolically active volume; OS: overall survival; CR: complete response; CT: chemotherapy; PFS: progression-free survival; ORR: objective response rate; GEM: gemcitabine; SD: stable disease; ADV: advanced; Nab-P: nab-paclitaxel; MMR: mismatch repair; CTLA-4: cytotoxic T-lymphocyte ntigen 4; MSLN: mesothelin; CIK: cytokine-induced killer; CEA: carcinoembryonic antigen; DCs: dendritic cells; APCs: antigen-presenting cells; GM-CSF: granulocyte-macrophage colony stimulating factor; CAR: chimeric antigen receptor