Table 1.
Target, indication, and development stage of therapeutic agents against metastatic cancers
| Target | Cancer type | Latest stage | Survival benefit (i) or best efficacy (ii and iii) | Safety concerns | Citation or Trial | Status (Oncology) | |
|---|---|---|---|---|---|---|---|
| i. Select therapies approved in the metastatic setting | |||||||
| zoledronate | Osteoclasts | Breast | Phase III | Disease-free survival (HR: 0.66) | Osteonecrosis of the jaw | Brufsky et al. 2015 | NDA approval |
| denosumab | RANKL | Breast | Phase III | Disease-free survival (HR: 0.82) | Well-tolerated | NCT00556374 | BLA approval |
| tazemetostat | EZH2 | Epitheloid sarcoma (INI1-) | Phase II * | No OS endpoint | Asthenia/Anemia/Nausea | NCT02601950 | NDA approval |
| sacituzumab govitecan-hziy | TROP2 ADC | Breast (TNBC) | Phase II * | No OS endpoint | Myelotoxicity | NCT01631552 | BLA approval |
| ado-trastuzumab emtansine | HER2 ADC | Breast | Phase III | OS benefit vs Her2 mAb + Chemo (HR: 0.68) | Thrombocytopenia and Hepatotoxicity | NCT00829166 | BLA approval |
| olaparib | PARP | Ovarian | Phase III | OS benefit vs placebo (0.74) | Fatigue, Diarrhea and hypertension | NCT01874353 | NDA approval |
| vismodegib | SMO | Basal cell carcinoma | Phase II * | No OS endpoint | Pneumonia and syncope | NCT00833417 | NDA approval |
| pembrolizumab | PD-1 | Melanoma | Phase III | OS benefit vs Ipilimumab (HR:0.68) | Colitis, diarrhea, fatigue, hepatotox | NCT01866319 | BLA approval |
| ii. Investigational tumor-intrinsic targets | |||||||
| demcizumab | DLL4 (Notch) | Metastatic NSCLC | Phase II | 50% ORR | Severe cardiac toxicity | NCT01189968 | Terminated |
| tarextumab | Notch2/3 (Notch) | Metastatic PDAC | Phase II | Reduced OS | Severe GI toxicity | NCT01647828 | Terminated |
| rovalpituzumab tesirine | DLL3-ADC (Notch) | SCLC | Phase II | Terminated | Significant Grade 3–5 toxicity | NCT02674568 | Terminated |
| ipafricept | Wnt8 (Wnt) | Ovarian | Phase I | Terminated | Significant bone toxicity | NCT02092363 | Terminated |
| vantictumab | FZD1,2,5,7 (Wnt) | Metastatic PDAC | Phase I | Terminated | Significant bone toxicity | NCT02005315 | Terminated |
| fresolimumab | TGF-β | Melanoma and RCC | Phase I | <5% ORR | Reversible keratoacanthomas | NCT00356460 | Terminated |
| galunisertib | ALK5 (TGF-β) | metastatic PDAC | Phase II | DCR: 25% | Neutropenia and Hepatotoxicity | NCT02734160 | Combination trials |
| decitabine | DNMT1–4 | Metastatic prostate | Phase II | PR: 17% | Neutropenia | Thibault et al 1998 | Combination trials |
| tucidinostat | HDAC class 1 | Advanced HR+ breast | Phase III | PFS (HR: 0.75) | Neutropenia | NCT02482753 | Unknown |
| metarrestin | Perinucleolar envelope | Advanced solid tumors | Phase I | TBD | TBD | NCT04222413 | In development |
| nirogacestat | γ-secretase (Notch) | Desmoid | Phase III | TBD | TBD | NCT03785964 | In development |
| iii. Investigational immune activating strategies | |||||||
| NC318 | Siglec-15 | Advanced solid tumors | Phase II | TBD | TBD | NCT03665285 | In development |
| eftilagimod alpha | LAG3 | metastatic breast | Phase I | 50% ORR w/taxol | Asthenia | NCT00349934 | In development |
| tiragolumab | TIGIT | NSCLC | Phase II | TBD | TBD | NCT04294810 | In development |
| epacadostat | IDO1 | Melanoma | Phase III | None | None | NCT02752074 | Terminated |
| MBG453 | TIM3 | Advanced solid tumors | Phase II | TBD | Fatigue | NCT02608268 | In development |
| JNJ-61610588 | VISTA | Advanced solid tumors | Phase I | Terminated | Terminated | NCT02671955 | Terminated |
| Enoblituzumab | B7-H3 | Advanced solid tumors | Phase I | SD reported | Fatigue and infusion reactions | NCT01391143 | In development |
| Hu5F9-G4 | CD47/SIRP1 | Advanced solid tumors | Phase I | None | Myelotoxicity | NCT02216409 | In development |
| IPH5201 | CD39/73 | Advanced solid tumors | Phase I | TBD | TBD | NCT04261075 | In development |
*
single arm; TBD: to be determined