Table 1.
Ongoing trials evaluating activity and efficacy of PARP inhibitors in PC (Clinicaltrials.gov last accessed 10 June 2021).
| Target | Tumor | Setting | Treatment Arms | Phase | Primary Outcome | N of Patients | clinicaltrial.gov Identifier |
|---|---|---|---|---|---|---|---|
| PARP | PC | Advanced, pretreated, without germline BRCA1/2 mutations but with BRCAness phenotype | olaparib | II | ORR | 34 | NCT02677038 |
| PARP | AST | Advanced, pretreated | (1) AZD6738 | II | ORR | 68 | NCT03682289 |
| ATR | (2) AZD6738 + olaparib | ||||||
| PARP | AST | Advanced, pretreated | cediranib + olaparib | II | ORR | 126 | NCT02498613 |
| VEGF | |||||||
| PARP | PC | Advanced, with BRCA1/2 or PALB2 mutation | (1) veliparib + gemcitabine hydrochloride + cisplatin | II | ORR Dose-finding | 107 | NCT01585805 |
| (2) gemcitabine hydrochloride + cisplatin | |||||||
| (3) veliparib | |||||||
| PARP | PC | Metastatic, untreated, with HRD | rucaparib + nal-IRI, leucovorin, fluorouracil | II | ORR | 110 | NCT03337087 |
| DLTs | |||||||
| PARP | AST | Advanced, pretreated, with HRD | rucaparib | II | ORR | 220 | NCT04171700 |
| PARP | PC | Advanced, pretreated, with BRCA1/2, PALB2, CHEK2 or ATM mutation | niraparib | II | PFS | 32 | NCT03601923 |
| PARP | PC | Advanced, pretreated | niraparib + dostarlimab + RT | II | DCR | 25 | NCT04409002 |
| PARP | PC | Advanced, pretreated, with DDR genes alteration | niraparib | II | ORR | 18 | NCT03553004 |
| PARP | PC | Advanced, following platinum-based CT without PD | (1) niraparib + nivolumab | Ib/II | PFS | 84 | NCT03404960 |
| (2) niraparib + ipilimumab | |||||||
| PARP | PC | Resected, after completion of (neo)adjuvant CT (+/− RT), with BRCA1/2 or PALB2 mutation | (1) olaparib (2) placebo | II | RFS | 152 | NCT04858334 |
| PARP | PC | metastatic, following platinum-based CT without PD, with BRCA1/2 mutation | (1) olaparib + pembrolizumab (2) olaparib | II | PFS | 88 | NCT04548752 |
| PD-1 | |||||||
| PARP, PD-1 | PC | Metastatic, pretreated, with BRCA1/2, PALB2, BARD1, RAD51c/d mutation | niraparib + dostarlimab | II | DCR | 20 | NCT04493060 |
| PARP, PD-1 | PC | metastatic, untreated, following low-dose CT with gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) | olaparib + pembrolizumab | II | PFS | 38 | NCT04753879 |
| PARP | PC | Advanced, untreated, with BRCA1/2 or PALB2 mutation | (1) fluzoparib + mFOLFIRINOX followed by fluzoparib maintenance | Ib/II | DLTs MTD ORR |
66 | NCT04228601 |
| (2) placebo + mFOLFIRINOX followed by placebo maintenance | |||||||
| WEE1 | PC | Metastatic, untreated | (1) adavosertib (MK-1775) + nab-paclitaxel + gemcitabine | I/II | MTD PFS |
133 | NCT02194829 |
| (2) placebo + nab-paclitaxel + gemcitabine | |||||||
| RAD51 | AST | Advanced, any line | CYT-0851 | I/II | DLTs ORR |
165 | NCT03997968 |
AST: advanced solid tumor; PC: pancreatic cancer; N: number; PFS: progression-free survival; OS: overall survival; DLTs: dose-limiting toxicities; MTD: maximum-tolerated dose; ORR: objective response rate; DDR: DNA damage response and repair; RT: radiation therapy; RFS: relapse free survival; RP2D: recommended phase 2 dose; HRD: homologous repair deficiency; PARP: poly ADP-ribose polymerase; ATR: ataxia telangiectasia and rad3-related; PD-1: programmed death-1; PD-L1: programmed death ligand 1; VEGF: vascular endothelial growth factor; PD: progressive disease; DCR: disease control rate; mFOLFIRINOX: modified FOLFIRINOX.