Table 4. Molecules moved from preclinical research to clinical development.
| Class | Drug(s) | Target | Phase | Enrollment or estimated | Primary endpoint subjects | Trial status | Trial IDa |
|---|---|---|---|---|---|---|---|
| γ-secretase inhibitors | MK0752 | γ-secretase | I | 5 | Safety/efficacy; relapsed or refractory TALL/T-LL | Terminated | NCT00100152 |
| MK0752 | I | 103 | Safety/MTD; advanced breast cancer/advanced solid tumors | Completed | NCT00106145 | ||
| MK0752 | I | 33 | Safety; recurrent or refractory CNS malignancies | Terminated | NCT00572182 | ||
| MK0752 + docetaxel | I/II | 30 | DLT; locally advanced or metastatic breast cancer | Completed | NCT00645333 | ||
| MK0752 + gemcitabine | I/IIa | 60 | Safety/MTD; stage IV pancreatic cancer | Recruiting | NCT01098344 | ||
| MK0752 | I | 30 | Notch response signature; healthy young adults | Completed | NCT00803894 | ||
| MK0752 | Pre-surgical | 20 | Safety/tolerability; early stage ER-positive breast cancer | Unknown | NCT00756717 | ||
| RO492909b | – | – | Safety/DLT; advanced solid Tumors/TALL/T-LL | Terminated | – | ||
| PF03084014 | I | 60 | Ongoing | NCT00878189 | |||
| BMS-906024 | I | 95 | Safety/tolerability; advanced solid tumors | Recruiting | NCT01292655 | ||
| BMS-906024 | I | 42 | Safety/tolerability; T-ALL/T-LL | Recruiting | NCT01363817 | ||
| BMS906024 + chemotherapyc | Ib | 60 | Safety; advanced or metastatic solid tumors | Recruiting | NCT01653470 | ||
| LY3039478 | I | 80 | DLTs; advanced or metastatic cancer | Recruiting | NCT01695005 | ||
| mAbs to Notch receptors or ligands | OMP-59R5 | Notch2/3 | I | 44 | Safety; advanced solid tumors | Recruiting | NCT01277146 |
| OMP-59R5 + Nab-P & gemcitabine | Notch2/3 | Ib/II | 154 | DLT/MTD; first line for stage IV pancreatic cancer | Recruiting | NCT01647828 | |
| OMP21M18 | DLL4 | I | 30 | Safety; advanced solid tumors | Recruiting | NCT00744562 | |
| OMP21M18 + FOLFIRIc | DLL4 | Ib | 32 | MTD; first or second line for advanced colorectal cancer | Recruiting | NCT01189942 | |
| OMP21M18 + CPc | DLL4 | Ib | 32 | MTD; first line for advanced non-squamous NSCLC | Recruiting | NCT01189968 | |
| OMP21M18 + gemcitabine | DLL4 | Ib | 40 | MTD; first line for advanced or metastatic pancreatic cancer | Recruiting | NCT01189929 | |
| REGN421 | DLL4 | I | 80 | Safety/tolerability; advanced solid tumors | Recruiting | NCT00871559 | |
| OMP52M51 | Notch1 | I | 33 | Safety; relapsed or refractory solid tumors | Recruiting | NCT01778439 |
a, clinical trial registration and information at www.clinicaltrials.gov; b, clinical trials with RO4929097 are not shown due to the termination of its development; c, chemotherapy, weekly paclitaxel, FOLFIRI or carboplatin plus paclitaxel. FOLFIRI, FOLolinic acid (leucovorin), 5-Fluorouracil (5-FU) plus IRInotecan (irinotecan) or carboplatin plus paclitaxel; CP, carboplatin and pemetrexed; Nab-P, nab-paclitaxel; TTP, time to progression; MTD, maximum tolerated dose; NSCLC, non-small cell lung cancer; CNS, central nervous system; T-ALL, T-acute lymphoblastic leukemia; T-LL, T-cell lymphoblastic lymphoma.