Table 1.
Ongoing Immunotherapy-Based Trials in PDAC. All data acquired from ClinicalTrials.gov.
| NCT | Phase | Intervention | Study Participant | Study Initiation |
|---|---|---|---|---|
| NCT00669734 | I | Single Arm: Falimarev (recombiant fowlpox CEA-expressing viral vector vaccine) + Inalimarev (recombinant vaccinia CEA-expressing viral vector vaccine) + Sargramostim | n = 18 locally advanced or metastatic PDAC | 2010– |
| NCT01595321 | II | Arm A: SBRT + FOLFIRINOX Arm B: SBRT + modified FOLFIRINOX Arm C: CY + GVAX + SBRT + modified FOLFIRINOX |
n = 19 surgically resected PDAC with no prior treatment | 2012– |
| NCT02451982 | II | Arm A: GVAX + CY Arm B: GVAX + Nivolumab + CY Arm C: GVAX + Nivolumab + Urelumab (anti-CD137) + CY Arm D: Nivolumab + BMS-986253 (anti-IL8) |
n = 76 surgically resectable PDAC | 2016– |
| NCT03104439 | II | Single Arm: Nivolumab + Ipilimumab + Radiation | n = 80 CRC and PDAC with prior chemotherapy treatment | 2017– |
| NCT03193190 | I, II | Arm A: GnP Arm B: Atezolizumab (anti-PD-L1) + Selicrelumab (agonist CD40 Ab) + GnP Arm C: Atezolizumab + Bevacizumab (anti-VEGF-A) + GnP Arm D: Atezolizumab + AB928 (dual adenosine receptor antagonist) + GnP Arm E: Atezolizumab + Tiragolumab (anti-TIGIT) + GnP Arm F: Atezolizumab + Cobimetinib (Anti-MEK) Arm G: Atezolizumab + PEGPH20 Arm H: Atezolizumab + BL-8040 (CXCR4 antagonist) Arm I: Atezolizumab + RO6874281 (immunocytokine-targeting FAP) Arm J: Atezolizumab + Tocilizumab (anti-IL-6 mAb) + GnP |
n = 340 metastatic PDAC with either no prior treatment (Arm 1) or disease progression following first-line systemic therapy (Arm 2) | 2017– |
| NCT03080974 | II | Single Arm: IRE + adjuvant Nivolumab | n = 10 locally advanced PDAC | 2017– |
| NCT03323944 | I | Single Arm: anti-mesothelin CAR vector-transduced autologous T-lymphocytes | n = 18 unresectable or metastatic PDAC | 2017– |
| NCT03269526 | I, II | Single Arm: anti-EGFR-armed activated T cells (EGFR BATs) + SoC | n = 22 locally advanced or metastatic pancreatic cancer who have received at least one dose of first-line chemotherapy | 2017– |
| NCT03153410 | I | Single Arm: CY + GVAX + Pembrolizumab + IMC-CS4 (anti-CSF1R Ab) | n = 12 borderline resectable PDAC | 2018– |
| NCT03607890 | II | Arm A: Nivolumab + Relatimab (Anti-LAG-3 Ab), coadministration Arm B: Nivolumab + Relatimab, sequential administration |
n = 42 metastatic or locally advanced PDAC, received prior PD-1 therapy, mismatch repair-deficient disease | 2018– |
| NCT03257761 | I | Single Arm: Durvalumab + guadecitabine (antimetabolite) | n = 55 advanced HCC, PDAC, BC | 2018– |
| NCT03563248 | II | Arm A: FOLFIRINOX + SBRT + surgical resection Arm B: FOLFIRINOX + Losartan + SBRT + surgical resection Arm C: FOLFIRINOX + Losartan + Nivolumab + SBRT + surgical resection Arm D: FOLFIRINOX + Nivolumab + SBRT + surgical resection |
n = 168 borderline resectable and locally advanced PDAC | 2018– |
| NCT03404960 | I, II | Arm A: Niraparib (PARP inhibitor) + Nivolumab Arm B: Niraparib + Ipilimumab |
n = 104 advanced PDAC that has not progressed on platinum-based therapy | 2018– |
| NCT03496662 | I, II |
Arm A: BMS-813160 (CCR2/CCR5 Inhibitor) + Nivolumab + GnP Arm B: GnP |
n = 40 borderline resectable and locally advanced PDAC | 2018– |
| NCT03592888 | I | Single Arm: Mature dendritic cell (mDC3/8) vaccine primer and booster | n = 29 resected PDAC with KRAS(G12D), KRAS(G12V), KRAS(G12R), KRAS(G12C-mutated), HLA-A02, HLA-A03, HLA-A11, HLA-B07, HLA-C08 | 2018– |
| NCT03006302 | II | Arm A: Epacadostat (IDO1 inhbitor) + Pembrolizumab + CRS-207 + CY + GVAX, on different dosages Arm B: Epacadostat + Pembrolizumab + CRS-207 on different dosages |
n = 41 metastatic PDAC that has progressed on prior chemotherapy | 2018– |
| NCT03829501 | I, II | Arm A: KY1044 (anti-ICOS) Arm B: KY1044 +Atezolizumab |
n = 280 metastatic solid tumors, including PDAC | 2019– |
| NCT03970252 | I | Single Arm: Nivolumab + mFOLFIRNOX pre-surgery | n = 28 borderline resectable PDAC | 2019– |
| NCT03682289 | II | Arm A: Ceralasertib (ATR kinase inhibitor) Arm B: Ceralasertib + Olaparib (PARP inhibitor) Arm C: Ceralasertib + Durvalumab |
n = 89 locally advanced or metastatic solid tumors, including PDAC | 2019– |
| NCT03816358 | I | Arm A: Anetumab Ravtansine (anti-mesothelin) + Nivolumab Arm B: Anetumab Ravtansine + Ipilimumab + Nivolumab Arm C: Anetumab Ravtansine + Nivolumab + Gemcitabine Hydrochloride |
n = 74 recurrent, unresectable, or metastatic mesothelin-positive PDAC | 2019– |
| NCT04137536 | I | Single Arm: EGFR BATs | n = 7 metastatic PDAC already treated with first-line standard chemotherapy | 2019– |
| NCT03745326 | I, II | Single Arm: anti-KRAS G12D murine TCR PBL cells + CY + Fludarabine (antimetabolite) + Aldesleukin (recombinant IL-2) | n = 70 metastatic or unresectable cancers with G12D mutated KRAS, NRAS or HRAS, HLA-A*11:01 positive, no prior therapy or nonresponders; PDAC, GI cancer, gastric cancer, colon cancer, rectal cancer | 2019– |
| NCT03806309 | II | Arm A: OSE2101 (T cell epitope-based vaccine) + FOLFIRI Arm B: FOLFIRI |
n = 106 HLA-A2 patients with locally advanced or metastatic PDAC not amenable to surgery | 2019– |
| NCT04161755 | I | Single Arm: RO7198457 (Personalized Tumor Vaccine) + Atezolizumab + mFOLFIRNOX | n = 29 resectable or radiographically resectable PDAC | 2019– |
| NCT03767582 | I, II | Arm A: GVAX + Nivolumab + SBRT + CCR2/CCR5 dual antagonist Arm B: Nivolumab + SBRT + CCR2/CCR5 dual antagonist |
n = 30 locally advanced unresectable PDAC | 2019– |
| NCT04390763 | II | Arm A: NIS793 (anti-TGF-β) + Spartalizumab + GnP Arm B: NIS973 + GnP Arm C: GnP |
n = 164 treatment naive, metastatic PDAC | 2020– |
| NCT04477343 | I | Single Arm: SX-682 (CXCR1/2 inhibitor) + Nivolumab as maintenance | n = 20 metastatic PDAC with 16+ weeks first-line chemo without evidence of progression | 2020– |
| NCT04612530 | I | Arm A: Nivolumab Arm B: Nivolumab + IRE Arm C: Nivolumab + IRE + TLR ligand (CpG) |
n = 18 primary oligometastatic PDAC | 2020– |
| NCT04493060 | II | Single Arm: Niraparib (PARP inhibitor) + Dostarlimab (anti-PD-1) | n = 22 germline or somatic BRCA and PALB2 metastatic PDAC | 2020– |
| NCT04672434 | I | Arm A: Sym024 (anti-CD73), tested at different dosages Arm B: Sym024 + Sym021 (anti-PD-L1), tested at different dosages |
n = 48 locally advanced or metastatic solid tumors, including PDAC | 2020– |
| NCT04365049 | observational | Arm A: Camrelizumab (PD-1) + Radiotherapy + GnP Arm B: GnP |
n = 100 locally advanced PDAC | 2020– |
| NCT04666740 | II | Arm A/B: Pembrolizumab + Olaparib in patients with homologous recombination mutations, with stable or responding disease on platinum therapy Arm C: Pembrolizumab + Olaparib in patients without homologous recombination mutations with platinum-sensitive disease |
n = 63 metastatic PDAC with responding disease on platinum-based treatment or homologous recombination gene deficiency | 2020– |
| NCT04581473 | I, II | Single Arm: Claudin 18.2-targeting autologous CAR-T cell injection (CT041) | n = 192 advanced PDAC or GEA positive for Claudin 18.2 who have failed at least 2 prior lines treatment, or patients with pathologically diagnosed advanced PDAC who have failed at least 1 prior line treatment | 2020– |
| NCT04157127 | I | Single Arm: Th-1 DC immunotherapy (autologous DC) vaccine | n = 43 potentially resectable PDAC following completion of standard chemotherapy | 2020– |
| NCT04627246 | I | Single Arm: PEP-DC (autologous DC vax loaded with personal peptides) + Nivolumab + SoC chemotherapy | n = 12 resectable PDAC | 2020– |
| NCT04753879 | II | Single Arm: Low-dose chemotherapy GAX-CI followed by Olaparib + Pembrolizumab | n = 38 untreated metastatic PDAC | 2021– |
| NCT04548752 | II | Arm A: Olaparib Arm B: Olaparib + Pembrolizumab |
n = 88 metastatic PDAC with germline BRCA 1/2 mutation | 2021– |
| NCT04940286 | II | Single Arm: Durvalumab + Oleclumab + GnP | n = 30 resectable or borderline resectable PDAC | 2021– |
| NCT04802876 | II | Arm A: Spartalizumab in patients with high PD-1 expression Arm B: Spartalizumab in patients with low PD-1 expression Arm C: Tislelizumab (anti-PD-1) in patient with high PD-1 expression |
n = 184 PD1-high mRNA expressing solid tumors, including PDAC | 2021– |
| NCT04888312 | Ib, II | Single Arm: Mitazalimab (anti-CD40) + FOLFIRINOX | n = 94 metastatic PDAC | 2021– |
| NCT04887805 | II | Single Arm: Pembrolizumab + Lenvatinib (TKI inhibitor) | n = 28 advanced unresectable PDAC | 2021– |
| NCT05000294 | I, II | Single Arm: Atezolizumab + Tivozanib (VEGF inhibitor) in immunologically cold tumors | n = 29 metastatic immunologically cold tumors, including PDAC | 2021– |
| NCT04146298 | I, II | Single Arm: Mutant KRAS G12V-specific TCR transduced T-cell therapy | n = 30 locally advanced or metastatic PDAC with KRAS G12V mutation and HLA-A*11:01 | 2021– |
| NCT05239182 | II | Single Arm: 9-ING-41 (GSK-3β inhibitor) + Retinfanlimab (anti-PD-1) + GnP | n = 32 previously untreated metastatic PDAC | 2022– |
| NCT05052723 | II | Single Arm: Pembrolizumab + Cabozantinib | n = 21 metastatic PDAC progressed on SoC | 2022– |
| NCT05132504 | II | Single Arm: mFOLFIRINOX + Pembrolizumab followed by surgery |
n = 30 resectable PDAC | 2022– |
| NCT05088889 | I | Single Arm: Ipilimumab + Nivolumab + SBRT + low dose irradiation | n = 10 metastatic PDAC | 2022– |
| NCT05102721 | I, II | Single Arm: Avelumab (anti-PD-1) + Pepinemab (anti-SEMA4D) | n = 48 metastatic PDAC after progression on first-line chemotherapy | 2022– |
| NCT05239143 | I | Single Arm: P-MUC1-Allogenic CAR-T cells (targeting the Mucin 1 antigen) | n = 180 advanced or metastatic epithelial-derived solid tumors refractory to SoC, including PDAC | 2022– |
| NCT05194735 | I, II | Arm A: TCR-T cell (sleeping beauty transposon/transposase to express TCRs against neoantigens) Arm B: TCR-T cell + IL 2 |
n = 180 with solid tumors who are TCR-applicable, completed HLA typing, and progressed on at least SoC therapy, including PDAC | 2022– |
| NCT05014776 | II | Single Arm: Tadalafil (PDE5 inhibitor) + Pembrolizumab + Ipilimumab + CRS-207 (Listeria vaccine) | n = 17 previously treated metastatic PDAC | 2022– |
| NCT06005493 | I, II | Arm A: AZD5863 (CLDN18.2) Intravenous Arm B: AZD5863 Subcutaneous |
n = 200 locally advanced or metastatic tumor expressing Claudin 18.2; PDAC, gastric cancer, GEA | 2023– |
| NCT05482893 | I, II | Arm A: PT886 (CLDN18.2, CD47) dose escalation Arm B: PT886 (ClLDN18.2, CD47) dose expansion Arm C: PT886 + GnP Arm D: PT886 + Pembrolizumab + oxaliplatin + leucovorin + Fluorouracil + capecitabine |
n = 114 unresectable or metastatic PDAC and GEA | 2023– |
| NCT05604560 | II | Single Arm: Tislelizumab and SX-682 (CXCR1/2 inhibitor) | n = 25 patients with resectable PDAC | 2023– |
| NCT05945823 | II | Single Arm (For PDAC): Pembrolizumab + Futibatinib (FGER1-4 inhibitor) + mFOLFIRINOX | n = 66 locally advanced or metastatic solid tumors, including PDAC | 2023– |
| NCT05630183 | II | Arm A: Botensilimab (CTLA-4 inhibitor) + GnP Arm B: GnP |
n = 78 metastatic PDAC with progression on FOLFIRINOX | 2023– |
| NCT06060405 | II | Single Arm: Durvalumab and Oleclumab | n = 22 resectable PDAC | 2023– |
| NCT06051851 | II | Arm A: Penpulimab (anti-PD-1) and Anlotinib (multitargetting TKI) + GnP Arm B: GnP |
n = 177 untreated metastatic PDAC | 2023– |
| NCT05558982 | II | Single Arm: BXCL701 (DPP inhibitor) + Pembrolizmab | n = 43 metastatic PDAC refractory to SoC | 2023– |
| NCT05846516 | I | Arm A: VSV-GP154 (chimeric oncolytic vesicular stomatitis virus vaccine with undisclosed peptides) + ATP150 (undisclosed protein vaccine) + ATP152 (undisclosed protein vaccine) Arm B: VSV-GP154 + ATP150 + ATP152 + Ezabenlimab (anti-PD-1) |
n = 85 KRAS G12D or KRAS G12V-mutated advanced or metastatic PDAC | 2023– |
| NCT05968326 | II | Arm A: Autogene Cevumeran (individualized neoantigen vaccine) + Atezolizumab + mFOLIRINOX Arm B: mFOLFIRINOX |
n = 260 resected T1–T3, N0–N2, M0 PDAC with no prior systemic treatment | 2023– |
| NCT05927142 | I, II | Single Arm: Durvalumab with Rintatolimod (TLR-3 agonist) | n = 43 stable metastatic PDAC | 2024– |
| NCT06158139 | I | Single Arm: Autologous CAR-T targeting the B7-H3 antigen | n = 27 B7-H3 antigen-positive PDAC refractory to SoC | 2024– |
| NCT06015724 | II | Single Arm: Daratumumab (anti-CD38) + KRAS vaccine + Nivolumab | n = 54, advanced PDAC or NSCLC with mutated KRAS G12A, C, D, R, S, V, or KRAS G13D and failed one prior treatment | 2024– |
Ab: antibody, ATR: ataxia telangiectasia and Rad30-related, B7-H3: B7 homolog 3 protein, BATs: bispecific antibody-armed activated T cells, BC: breast cancer, BRCA: breast cancer gene, CEA: carcinoembryonic antigen, CRC: colorectal cancer, CSF1R: colony-stimulating factor 1 receptor, DPP: dipeptidyl peptidases, EGFR: epidermal growth factor receptor, FAP: fibroblast activation protein–a, FGFR: fibroblast growth factor receptor, FOLFIRI: 5-fluorouracil, leucovorin, irinotecan, GAX-CI: gemcitabine, nab-paclitaxel, capecitabine, cisplatin, irinotecan, GEA: gastroesophageal adenocarcinoma, GI: gastrointestinal, GSK-3β: glycogen synthase kinase-3β, HCC: hepatocellular carcinoma, HLA: human leukocyte antigen, HRAS: Harvey rat sarcoma virus, ICOS: inducible T-cell co-stimulator, IDO1: indoleamine 2,3-dioxygenase-1 inhibitor, IL: interleukin, LAG-3: lymphocyte activation gene-3, mAb: monoclonal antibody, MEK: mitogen-activated extracellular signal-regulated kinase, mFOLFIRINOX: modified FOLFIRINOX, MUC1: Mucin 1, NRAS: neuroblastoma rat sarcoma virus, PARP: poly(ADP-ribose) polymerase, PALB2: partner and localizer of BRCA2, PBL: peripheral blood lymphocyte, SEMA4D: semaphorin 4D, TCR: T-cell receptor, TIL: tumor-infiltrating lymphocytes, TKI: tyrosine kinase inhibitor, TGF-β: transforming growth factor β, TIGIT: T-cell immunoglobulin and ITIM domain, VEGF: vascular endothelial growth factor.