Table 2.
Ongoing trials evaluating activity and efficacy of novel molecules acting on different targets in PC (Clinicaltrials.gov last accessed 10 June 2021).
| Target | Tumor | Setting | Treatment Arms | Phase | Primary Outcome | N of Patients | clinicaltrial.gov Identifier |
|---|---|---|---|---|---|---|---|
| FAK PD-1 |
PC | Resectable | (1) perioperative CT followed by pembrolizumab + defactinib (2) perioperative CT followed by pembrolizumab |
II | pCR rate | 36 | NCT03727880 |
| FAK | PC | Locally advanced | (1) CT followed by SBRT + defactinib (2) CT followed by SBRT alone |
II | PFS | 42 | NCT04331041 |
| MEK FAK |
PC | Advanced, pretreated | GSK2256098 + trametinib | II | ORR | 16 | NCT02428270 |
| MEK BCL-2 |
AST | Advanced, pretreated, with KRAS or NRAS mutation | trametinib + navitoclax | Ib/II | ORR PFS Safety |
130 | NCT02079740 |
| MEK BRAF |
PC | Advanced, pretreated, with BRAF V600E mutation | binimetinib + encorafenib | II | ORR | 29 | NCT04390243 |
| ERK | PC | Metastatic, pretreated | (1) LY3214996 + hydroxychloroquine (2) LY3214996 |
II | DCR, Safety |
52 | NCT04386057 |
| ALK5 | PC | Metastatic, pretreated | TEW-7197 + FOLFOX | Ib/II | PFS | 36 | NCT03666832 |
| EGFR | PC | Advanced, pretreated | CT followed by anti-CD3 x anti-EGFR bispecific antibody armed activated T cells | I/II | OS Safety |
22 | NCT03269526 |
| EGFR HDAC |
PC | advanced, first-line | CG200745 PPA + gemcitabine + erlotinib | I/II | ORR | 24 | NCT02737228 |
| EGFR | PC | Resected, adjuvant | (1) CT (2) gemcitabine + erlotinib |
II/III | OS | 545 | NCT01013649 |
| CTGF | PC | Locally advanced, neoadjuvant | (1) pamrevlumab + gemcitabine + nab-paclitaxel (2) placebo + gemcitabine + nab-paclitaxel |
III | OS Proportion of R0 or R1 resection |
256 | NCT03941093 |
| KRAS | PC | Advanced, pretreated | cyclophosphamide + fludarabine + T cell therapy (+ anti-PD-1) | I/II | ORR Safety |
30 | NCT04146298 |
| KRAS | AST | Advanced, pretreated, with KRAS G12C mutation | adagrasib | I/II | ORR Safety Plasma concentration |
391 | NCT03785249 |
| KRAS NRAS |
AST | Detectable ctDNA despite prior therapy, with KRAS/NRAS mutation | ELI-002 | I/II | MTD RFS Safety |
159 | NCT04853017 |
| HER2 | AST | Advanced, pretreated, with HER2 expression or amplification | A166 | I/II | MTD ORR |
82 | NCT03602079 |
| HDAC PD-1 |
PC CC |
Advanced pretreated | entinostat + nivolumab | II | ORR | 44 | NCT03250273 |
| XPO1 | PC | Metastatic, untreated | (1) selinexor + gemcitabine/nab-paclitaxel gemcitabine/nab-paclitaxel |
I/II | MTD OS Safety |
56 | NCT02178436 |
| NTRK ROS1 ALK |
AST | Advanced, with NTRK/ROS1/ALK gene rearrangement | entrectinib | II | ORR | 300 | NCT02568267 |
| NTRK | AST | Advanced, pretreated, with NTRAK gene rearrangement | larotrectinib | II | ORR | 203 | NCT02576431 |
| Metabolism | PC | Metastatic, untreated | (1) devimistat + FOLFIRINOX(2) FOLFIRINOX | III | ORR PFS |
500 | NCT03504423 |
AST: advanced solid tumor; PC: pancreatic cancer; CC: cholangiocarcinoma; N: number; PFS: progression-free survival; OS: overall survival; DLTs: dose-limiting toxicities; MTD: maximum-tolerated dose; ORR: objective response rate; RT: radiation therapy; RFS: relapse free survival; ctDNA: circulating tumor DNA; FAK: focal adhesion kinase-1; HDAC: histone deacetylase; PD-1: programmed death-1; PD: progressive disease; DCR: disease control rate; pCR: pathologic complete response; XPO1: exportin 1; EGFR: epidermal growth factor receptor; NTRK: neurotrophic tyrosine receptor kinase; ALK: anaplastic lymphoma kinase; ROS1: ROS proto-oncogene 1; KRAS: Kirsten rat sarcoma; NRAS: neuroblastoma RAS viral oncogene homolog; HER-2: human epidermal growth factor receptor 2; ERK: extracellular signal-regulated kinase; BRAF: B-RAF proto-oncogene; Bcl-2: B-cell lymphoma 2; CTGF: connective tissue growth factor.