Table 1.
Selected Clinical Trials With Targeted Therapeutics for the Management of Metastatic Pancreatic Cancer
| Drug | Target | Mechanism | Phase of Trial | Trial Design | Cancer Type | Primary Endpoint | Clinical Reference | Results | Adverse Events (Any Grade) | Current Status |
|---|---|---|---|---|---|---|---|---|---|---|
| Sotorasib | KRASG12C | Small molecule inhibitor of KRASG12C | I/II | Monotherapy or in combination with PD-1/PD-L1 inhibitors | Basket trial | Treatment-related adverse effects, objective response | NCT03600883 (CodeBreak 100) | 8 PR 21.1% ORR 32% DCR Median PFS 3.98 months Median OS 6.87 months |
Diarrhea (5.3%) Fatigue (5.3%) Abdominal pain (2.6%) |
Recruiting |
| Adagrasib | KRASG12C | Small molecule inhibitor of KRASG12C | I/II | Monotherapy or in combination with PD-1 or EGFR inhibitors | Basket trial | Treatment-related adverse effects, objective response | NCT03785249 (KRYSTAL-1) | 5 PR 100% DCR Median PFS 6.6 months |
Nausea (48%) Diarrhea (43%) Vomiting (43%) |
Recruiting |
| Olaparib | PARP | Small molecule inhibitor of PARP | III | Monotherapy or placebo | gBRCA mutated pancreatic cancer | Objective response | NCT02184195 | Median PFS 7.4 months Median OS 18.9 months Hazard Ratio 0.53 |
Fatigue (60%) Nausea (45%) Anemia (27%) |
Active, not recruiting |
| Rucaparib | PARP | Small molecule inhibitor of PARP | II | Monotherapy | BRCA1, BRCA2 or PALB2 mutated pancreatic cancer | Treatment-related adverse effects | NCT03140670 | Median PFS 13.1 months Median OS 23.5 months 41.7% ORR 66.7% DCR |
Anemia (74%) Nausea (48%) Increased ALT (47%) |
Active, not recruiting |
| Niraparib | PARP | Small molecule inhibitor of PARP | Ib/II | In combination with Ipilimumab or Nivolumab | Platinum-sensitive advanced pancreatic cancer | Treatment-related adverse effects, objective response | NCT03404960 | Niraparib + Nivolumab 6-month PFS 20.6% Niraparib + Ipilimumab 6-month PFS 59.6% |
Niraparib + Nivolumab Hypertension (8%) Anemia (4%) Thrombocytopenia (4%) Niraparib + Ipilimumab Fatigue (14%) Anemia (11%) |
Active, not recruiting |
| Entrectinib | TRK, ROS1 and ALK | Small molecule inhibitor of TRK, ROS1 and ALK | II | Monotherapy | Basket trial | Objective response | NCT02568267 | 2 PR 1 SD |
Arthralgias Myalgias Fatigue |
Recruiting |
| Zenocutuzumab | HER2 and HER3 | IgG1 bispecific antibody targeting HER2 and HER3 | I/II | Monotherapy | Basket trial | Objective response | NCT02912949 | ORR 39% | Asthenia, Diarrhea, Anemia Nausea |
Recruiting |
| Durvalumab and Tremelimumab | PD-L1 and CTLA4 | Monoclonal antibody against PD-L1 and CTLA4 | II | Combination therapy or placebo (in combination with Gemcitabine and Nab-Paclitaxel) | Metastatic pancreatic cancer | Objective response | NCT02879318 | Median OS 9.8 months Median PFS 5.5 months |
Fatigue (20%) Thromboembolic event (15%) Sepsis (11%) |
Active, not recruiting |
| Indoximod | IDO pathway | Small molecule inhibitor of IDO | I/II | In combination with Gemcitabine and Nab-Paclitaxel | Metastatic pancreatic cancer | Treatment-related adverse effects, objective response | NCT02077881 | ORR 46.2% CR 1% PR 45.2% Median OS 10.9 months |
Fatigue Nausea Anemia |
Completed |
| Tarextumab | Notch Signaling | Monoclonal antibody against Notch receptor | Ib/II | Monotherapy or placebo (in combination with nab-paclitaxel and gemcitabine) | Previously untreated stage 4 pancreatic cancer | Treatment-related adverse effects, objective response | NCT01647828 | Median OS 6.4 months Median PFS 3.7 months ORR 20.2% |
Diarrhea (72%) Fatigue (52%) Thrombocytopenia (49%) |
Completed |
| Vismodegib | Hedgehog Pathway | Small molecule inhibitor of PTCH and SMO | Ib/II | Monotherapy or placebo (in combination with gemcitabine) | Metastatic pancreatic cancer | Objective response | NCT01064622 | Median PFS 4.0 months Median OS 6.9 months PR 8% SD 51% |
Neutropenia (28%) Fatigue (13%) Anorexia (9%) |
Completed |
| PEGPH20 | Hyaluronic Acid | Recombinant form of human hyaluronidase | Ib/II | Monotherapy or placebo (in combination with FOLFIRINOX) | Metastatic pancreatic cancer | Treatment-related adverse effects, objective response | NCT01959139 | Median OS 7.7 months Median PFS 4.3 months RR 33% |
Nausea (25%) Diarrhea (24%) Vomiting (22%) |
Active, not recruiting |