evofosfamide
Evofosfamide, formerly known as TH-302 is an investigational new drug that is being evaluated for the treatment of multiple tumor types, including pancreatic cancer, soft tissue sarcoma, and multiple myeloma, often in combination with other therapies. It is a hypoxia-activated prodrug designed to target and kill hypoxic cells within tumors. It functions by releasing the DNA crosslinking agent bromo-isophosphoramide mustard under low oxygen conditions, making it potentially effective against tumor regions where standard chemotherapy and radiation therapies are less effective due to hypoxia. — Wikipedia
Clinical trial activity
26 trials · 27 clinical orgs · 0 marketing orgs
Earliest trial started Jun 1, 2007 (NCT00495144)
Timeline
Indications
Studied for
- Biliary Tract Neoplasms · Phase 2
- Carcinoma, Hepatocellular · Phase 1
- Carcinoma, Non-Small-Cell Lung · Phase 2
- Carcinoma, Renal Cell · Phase 1
- Esophageal Neoplasms · Phase 1
- Gastrointestinal Stromal Tumors · Phase 1
- Glioblastoma · Phase 2
- Glioma · Phase 2
- Hypoxia · Phase 1
- Kidney Neoplasms · Phase 1/Phase 2
- Leukemia, Lymphocytic, Chronic, B-Cell · Phase 1
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive · Phase 1
- Leukemia, Myeloid, Acute · Phase 1
- Liver Neoplasms · Phase 1/Phase 2
- Melanoma · Phase 2
- Multiple Myeloma · Phase 1/Phase 2
- Myelodysplastic Syndromes · Phase 1
- Neoplasms · Phase 1
- Neuroendocrine Tumors · Phase 2
- Pancreatic Neoplasms · Phase 3
- Precursor Cell Lymphoblastic Leukemia-Lymphoma · Phase 1
- Primary Myelofibrosis · Phase 1
- Prostatic Neoplasms · Phase 1/Phase 2
- Sarcoma · Phase 3
- Squamous Cell Carcinoma of Head and Neck · Phase 1
Mechanism of action
- DNAINHIBITOR
DNA inhibitor
Activated by a process that involves a 1-electron reduction mediated by ubiquitous cellular reductases to generate a radical anion prodrug (RP). When exposed to severe hypoxic conditions (<0.5% O2), the RP can either fragment directly or undergo further reduction at the nitroimidazole site of the prodrug, leading to fragmentation and the release of Bromo isophosphoramide mustard (Br-IPM), a potent DNA alkylating agent
Chemistry & pharmacology
SMILES
Cn1c(COP(=O)(NCCBr)NCCBr)cnc1[N+](=O)[O-]- Mol. weight
- 449.04 g/mol
- Lipinski Ro5
- Pass
- Rule of 3
- No
- Chirality
- Achiral Molecule
- Inorganic
- No
- Polymer
- No
Oral
No
Parenteral
No
Topical
No
Sources
- WikipediaEvofosfamide ↗
- ChEMBLCHEMBL260046 ↗
Also known as
- evofosfamide
- evofosfamide
- evofosfamide
- evofosfamide
- th 302
- th-302
- th-302
- th-302
- th-302
- th302 cpd
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT03098160 | Phase 1 | May 10, 2017 | Threshold Pharmaceuticals, University of Texas at Houston |
| NCT02712567 | N/A | Mar 9, 2016 | Sarcoma Alliance for Research through Collaboration, Threshold Pharmaceuticals |
| NCT02598687 | Phase 1 | Dec 1, 2015 | Maastricht University, Threshold Pharmaceuticals, Zuyderland Medisch Centrum |
| NCT02342379 | Phase 2 | May 1, 2015 | University of Texas, San Antonio |
| NCT02433639 | Phase 2 | Apr 1, 2015 | Merck Serono, Seoul National University |
| NCT02402062 | Phase 2 | Feb 1, 2015 | Grupo Espanol de Tumores Neuroendocrinos (GETNE), Pfizer, Threshold Pharmaceuticals |
| NCT01721941 | Phase 1 | Dec 1, 2014 | Scripps, Threshold Pharmaceuticals |
| NCT02255110 | Phase 2 | Dec 1, 2014 | Merck KGaA, Merck Serono, Threshold Pharmaceuticals |
| NCT02093962 | Phase 2 | Jun 1, 2014 | Merck Serono, Threshold Pharmaceuticals, University of California, Los Angeles |
| NCT02076230 | Phase 1 | Feb 1, 2014 | Merck KGaA, Threshold Pharmaceuticals |
| NCT02047500 | Phase 1 | Jan 1, 2014 | Merck Serono, Threshold Pharmaceuticals |
| NCT02020226 | Phase 1 | Nov 1, 2013 | Threshold Pharmaceuticals, University of Arizona |
| NCT01864538 | Phase 2 | May 1, 2013 | Threshold Pharmaceuticals |
| NCT01833546 | Phase 1 | Apr 1, 2013 | Merck KGaA, Merck Serono, Threshold Pharmaceuticals |
| NCT01746979 | Phase 3 | Dec 1, 2012 | Merck Serono, Threshold Pharmaceuticals |
| NCT01497444 | Phase 1/Phase 2 (Phase 2) | May 1, 2012 | Mayo Clinic, National Cancer Institute (NCI), Threshold Pharmaceuticals |
| NCT01522872 | Phase 1/Phase 2 (Phase 2) | Feb 1, 2012 | Threshold Pharmaceuticals |
| NCT01485042 | Phase 1 | Dec 1, 2011 | Duke University, GlaxoSmithKline, National Comprehensive Cancer Network, Threshold Pharmaceuticals |
| NCT01440088 | Phase 3 | Sep 1, 2011 | Cornell University, Sarcoma Alliance for Research through Collaboration, Threshold Pharmaceuticals |
| NCT01381822 | Phase 1 | Jun 1, 2011 | Indiana University, Threshold Pharmaceuticals, University of Iowa |
Organizations
Research & Development (27)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Threshold Pharmaceuticals | For profit | 23 | 12 | 4 | 2007 |
| Merck Serono | For profit | 6 | 2 | 3 | 2012 |
| Mayo Clinic | Academic/Hospital | 3 | 0 | 1 | 2008 |
| Merck KGaA | For profit | 3 | 3 | 2 | 2013 |
| Sarcoma Alliance for Research through Collaboration | Academic/Hospital | 2 | 1 | 2 | 2011 |
| SCRI Development Innovations | For profit | 2 | 0 | 2 | 2007 |
| University of Texas at Houston | Academic/Hospital | 2 | 0 | 1 | 2010 |
| University of Texas, San Antonio | Academic/Hospital | 2 | 2 | 1 | 2011 |
| Cornell University | Academic/Hospital | 1 | 0 | 1 | 2011 |
| Duke University | Academic/Hospital | 1 | 1 | 1 | 2011 |
| GlaxoSmithKline | For profit | 1 | 0 | 1 | 2011 |
| Grupo Espanol de Tumores Neuroendocrinos (GETNE) | Academic/Hospital | 1 | 1 | 1 | 2015 |
| Indiana University | Academic/Hospital | 1 | 0 | 1 | 2011 |
| Lousiana Health Sciences Center - Shreveport | Academic/Hospital | 1 | 0 | 1 | 2010 |
| Maastricht University | Academic/Hospital | 1 | 1 | 1 | 2015 |
| National Cancer Institute (NCI) | Government | 1 | 1 | 1 | 2012 |
| National Comprehensive Cancer Network | Academic/Hospital | 1 | 0 | 1 | 2011 |
| Pfizer | For profit | 1 | 0 | 1 | 2015 |
| Pharmaceutical Research Associates, Inc. (PRA) | For profit | 1 | 0 | 1 | 2010 |
| Scripps | Academic/Hospital | 1 | 1 | 1 | 2014 |