Table 1:
Selected Clinical Trials Examining Novel Immunotherapy Regimens in Patients with Pancreatic Ductal Adenocarcinoma
| Study NCT Registry Number | Study Agent(s) | Standard Agent(s) | Subjects | Treatment Setting | Phase | Status/Results |
|---|---|---|---|---|---|---|
| Multimodal IO Regimens | ||||||
|
NCT03329248
NCT03586869 |
Metronomic chemo (aldoxorubicin, gem, NP, oxal, 5FU, and cy) haNK aPD-L1 PD-L1 t-haNK |
SBRT | mPDAC | Metastatic ≤2nd line |
Ib/II | Closed mOS 8.0 mo mPFS 6.6 mo 1 CR (treated with PD-L1 t-haNK) |
| NCT04390399 | Aldoxorubicin N-803 (IL-15) PD-L1 t-haNK |
Chemo (gem+NP [1st line] or NAPOLI-1 [2nd line]) SBRT |
mPDAC | Metastatic Maintenance (group A) 2nd line (group B) ≤3rd line (group C) |
II | Open |
| NCT03767582 | CCR2/CCR5i aPD-1 ± GVAX |
Chemo SBRT |
LA-PDAC | Neoadjuvant & Adjuvant | II | Open |
| NCT03153410 | GVAX aPD1 CSF1Ri |
Chemo (neoadj) SBRT (neoadj) |
BR-PDAC | Neoadjuvant & Adjuvant | Pilot | Open |
| NCT03006302 | CRS-207 IDOi aPD-1 ± GVAX |
mPDAC | Metastatic ≤2nd line |
II | Open | |
| Anti-Tumor Vaccines | ||||||
| NCT04853017 | Peptide Vaccine (Shared Neoantigen [KRAS], adj AMP-CpG) | rPDAC [KRAS/N RAS mut] |
NED Maintenance | I/II | Open | |
| NCT03948763 | mRNA Vaccine (Shared Neoantigen [KRAS], lipid-based) ± aPD-1 |
mPDAC [mKRAS] | Not specified | I | Open | |
| NCT04799431 | Peptide vaccine (Personalized Neoantigen, adj pICLC) aPD-1 |
mPDAC | Maintenance | Pilot/I | Not yet Open | |
| NCT02600949 | Peptide vaccine (Personalized Neoantigen, adj imiquimod) | mPDAC | Maintenance ≤2nd Line |
Pilot | Open | |
| NCT03468244 | mRNA Vaccine (Personalized Neoantigen) | Advanced PDAC | ≤2nd Line | Pilot | Open | |
| NCT03592888 | Autologous DC Vaccine, (Shared KRAS Neoantigens) | rPDAC [mKRAS] | Adjuvant | I | Open | |
| NCT04627246 | Autologous DC Vaccine, (Personalized Neoantigen) aPD-1 |
Chemo | rPDAC | Adjuvant | I | Open |
| NCT04157127 | Autologous DC Vaccine* (Personalized Tumor Lysate, adj peg-IFN) *perinodal injection |
Chemo | rPDAC | Adjuvant | I | Open |
| NCT04111172 | TAA-encoding Viral Vaccine (Shared, adj il-PADRE [TH1 epitope]) | Chemo | rPDAC | Adjuvant | II | Open |
| NCT03806309 | Peptide vaccine (Shared TAA/TSA, adj il-PADRE [TH1 epitope) ± aPD-1 |
± FOLFIRI | LA or mPDAC | Maintenance | II | Open |
| NCT03376659 | TAA-encoding Viral Vaccine (Shared, adj TRICOM) + aPD-L1 |
Maintenance Chemo | mPDAC Maintenan ce |
Maintenance | II | Enrolled Prelim results expected soon |
| NCT03161379 | GVAX aPD1 |
Chemo SBRT |
BR-PDAC | Neoadjuvant | II | Open |
| NCT03190265 | CRS-207 aPD-1 aCTLA4 ± GVAX |
Chemo SBRT |
mPDAC | ≤2nd line | II | Open |
| NCT02451982 | GVAX a4-1BB aPD-1 |
Chemo SBRT |
rPDAC | Neoadjuvant & adjuvant | II | Open Prelim results expected soon |
| Immune Agonists and Adjuvants | ||||||
| NCT04807972 | aCD40 agonist ± aPD-1 |
Chemo | mPDAC | 1st Line | II | Open |
| NCT03329950 | aCD40 agonist ± aPD-1 ± FLT3L |
±Chemo | mPDAC | 1st line (aCD40 + Chemo arm) Refectory (other groups) |
I/II | Open |
| NCT03214250 | aCD40 agonist ± aPD-1 |
Chemo | mPDAC | 1st line | II | [Prelim] No improvement in PFS/OS/ORR when aCD40 added to SOC chemo + PD-1 |
| NCT03193190 | aCD40 agonist aPD-L1 |
Chemo | mPDAC | 2nd line | I/II | Open |
| NCT02376699 | aCD40 agonist aPD-1 |
Chemo | mPDAC | 1st Line | II | Enrolled Prelim results expected soon |
| NCT04387071 | aOX40 agonist + TLR9 adjuvant (intratumoral) | LA or mPDAC | 2nd Line | II | Not Yet Open | |
| NCT04612530 | Electroporation CpG adj aPD-1 |
mPDAC (hepatic mets) | Maintenance | I | Open | |
| NCT04050085 | TLR9 agonist (intratumoral) aPD-1 |
SBRT | mPDAC | Refractory | I | Open |
| NCT03983954 | Superantigen fAb aPD-L1 |
mPDAC | Refractory | I | Open | |
| NCT03225989 | TMZ-CD40L and 4–1BBL-encoded Virus | Chemo | LA or mPDAC | ≤1st line | I/II | Open |
| TME Cellular/Signaling Modulators | ||||||
| NCT04390763 | TGFβ antagonist ± aPD-1 |
Chemo | mPDAC | 1st line | II | Open |
| NCT03821935 | GARP-TGFβ1 antagonist ± aPD-1 |
LA or mPDAC | Refractory | I | Open | |
| NCT04581343 | aIL-1β antagonist aPD-1 |
Chemo | mPDAC | 1st line | I | Open |
| NCT04543071 | CXCR4i aPD-1 |
aPD1 Chemo | mPDAC | 1st line | II | Open |
| NCT02826486 | CXCR4i aPD-1 |
± Chemo | mPDAC | ≥2nd line | I/II | Enrolled [Prelim] DCR 77%, ORR 32% w/chemo DCR 34%, ORR 3% w/o chemo |
| NCT03193190 | CXCR4i aPD-L1 |
mPDAC | ≥2nd line | II | ||
| NCT04477343 | CXCR1|2i aPD-1 |
mPDAC | Maintenance | I | Open | |
| NCT03257761 | Epigenetic modifier (DNMTi) aPD-L1 |
mPDAC | ≥2nd line | Ib | Open | |
| NCT03250273 | Epigenetic modifier (HDACi) aPD-1 |
mPDAC | ≥2nd line | II | Enrolled Interim results expected soon |
|
| NCT04060342 | CD11b modulator ± aPD-1 |
± Chemo | mPDAC | 1st line (for chemo combo) | I/II | Open |
| NCT03193190 | aIL-6 antagonist aPD-L1 |
Chemo | mPDAC | 1st line | II | Open |
| NCT03727880 | FAKi aPD-L1 |
Chemo | rPDAC | Neoadjuvant & Adjuvant | II | Open |
| NCT03496662 | CCR2/CCR5i aPD-1 |
Chemo | BR or LA-PDAC | Neoadjuvant 1st line |
I/II | Open |
Key (selected terms): adj – vaccine/immune adjuvant; AMP-CpG – amphiphilic-CpG (pathogen-associated molecular pattern); BR-PDAC – borderline resectable pancreatic ductal adenocarcinoma; CRS-207 – live, attenuated double-deleted Listeria vaccine targeting mesothelin; CSF-1R, colony-stimulating factor-1 receptor; Cy – cyclophosphamide; DC – dendritic cell; DCR – disease control rate; DNMTi - DNA methyltransferase inhibitor; FAKi – focal adhesion kinase inhibitor; Gem – gemcitabine; GVAX - GM-CSF secreting allogeneic pancreatic tumor cell vaccine; haNK – high affinity natural killer cells; HDACi - histone deacetylase inhibitor; IDOi - indolamine 2,3-dioxygenase inhibitor; IO – immunotherapy, immuno-oncology; LA-PDAC – locally advanced pancreatic ductal adenocarcinoma; mPDAC – metastatic pancreatic ductal adenocarcinoma; NAPOLI-1- 5FU and leucovorin plus liposomal irinotecan; NP – nab-paclitaxel; ORR – objective responsive rate; OS – overall survival; Oxal – oxaliplatin; PD-L1 t-haNK – PD-L1 targeted high affinity natural killer cells; PFS – progression-free survival; pICLC - polyinosinic-polycytidylic acid; rPDAC– resected pancreatic ductal adenocarcinoma; SOC – standard of care; TAA – tumor-associated antigen; TLR – toll-like receptor; TME – Tumor Microenvironment; TSA – tumor-specific antigen or neoantigen.