EVOFOSFAMIDE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H16Br2N5O4P
Molecular Weight	449.036
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(COP(=O)(NCCBr)NCCBr)=CN=C1[N+]([O-])=O

InChI

InChIKey=UGJWRPJDTDGERK-UHFFFAOYSA-N

InChI=1S/C9H16Br2N5O4P/c1-15-8(6-12-9(15)16(17)18)7-20-21(19,13-4-2-10)14-5-3-11/h6H,2-5,7H2,1H3,(H2,13,14,19)

HIDE SMILES / InChI

Molecular Formula	C9H16Br2N5O4P
Molecular Weight	449.036
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27232101 | https://www.ncbi.nlm.nih.gov/pubmed/26094595 | http://mtem.com/etb-platform/evofosfamide/

Evofosfamide, also formerly known as TH-302, is an investigational hypoxia-activated prodrug and is used to target cancerous cells under hypoxic conditions, which is a feature possessed by multiple solid tumors including glioblastoma and pancreatic cancer. Within regions of tumor hypoxia, evofosfamide releases bromo isophosphoramide mustard (Br-IPM), a potent DNA alkylating agent that kills tumor cells by forming DNA crosslinks. Once activated in hypoxic tissues, Br-IPM can also diffuse into surrounding oxygenated regions of the tumor and kill cells there via a “bystander effect”. Because of its preferential activation in the targeted hypoxic regions of solid tumors, evofosfamide may be less likely to produce broad systemic toxicity seen with untargeted cytotoxic chemotherapies.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 282 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18257544	Crosslinking Agent 83

Conditions

Condition	Modality	Highest Phase	Product
Glioblastoma 66 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26094595	Primary	Phase II 1147	Unknown Approved Use Unknown
Pancreatic cancer 98 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27232101	Primary	Phase III 665	Unknown Approved Use Unknown
Soft tissue sarcoma 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28651927	Primary	Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
4.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	120 mg/m² 1 times / week multiple, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	240 mg/m² 1 times / week multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	480 mg/m² 1 times / week multiple, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	575 mg/m² 1 times / week multiple, intravenous dose: 575 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	670 mg/m² 1 times / week multiple, intravenous dose: 670 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	940 mg/m² 1 times / week multiple, intravenous dose: 940 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.06 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	120 mg/m² 1 times / week multiple, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.11 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	240 mg/m² 1 times / week multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.15 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	480 mg/m² 1 times / week multiple, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.19 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	575 mg/m² 1 times / week multiple, intravenous dose: 575 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.22 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	670 mg/m² 1 times / week multiple, intravenous dose: 670 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.37 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	940 mg/m² 1 times / week multiple, intravenous dose: 940 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
3.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	120 mg/m² 1 times / week multiple, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	240 mg/m² 1 times / week multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	480 mg/m² 1 times / week multiple, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	575 mg/m² 1 times / week multiple, intravenous dose: 575 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
23 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	670 mg/m² 1 times / week multiple, intravenous dose: 670 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
25.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	940 mg/m² 1 times / week multiple, intravenous dose: 940 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.08 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	120 mg/m² 1 times / week multiple, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.11 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	240 mg/m² 1 times / week multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.16 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	480 mg/m² 1 times / week multiple, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.26 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	575 mg/m² 1 times / week multiple, intravenous dose: 575 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.37 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	670 mg/m² 1 times / week multiple, intravenous dose: 670 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.54 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	940 mg/m² 1 times / week multiple, intravenous dose: 940 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
0.83 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	120 mg/m² 1 times / week multiple, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.98 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	240 mg/m² 1 times / week multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.98 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	480 mg/m² 1 times / week multiple, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.83 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	575 mg/m² 1 times / week multiple, intravenous dose: 575 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.84 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	670 mg/m² 1 times / week multiple, intravenous dose: 670 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	940 mg/m² 1 times / week multiple, intravenous dose: 940 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	EVOFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.81 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	120 mg/m² 1 times / week multiple, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.46 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	240 mg/m² 1 times / week multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.54 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	480 mg/m² 1 times / week multiple, intravenous dose: 480 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.67 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	575 mg/m² 1 times / week multiple, intravenous dose: 575 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.87 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	670 mg/m² 1 times / week multiple, intravenous dose: 670 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.61 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21415214/	940 mg/m² 1 times / week multiple, intravenous dose: 940 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	N,N'-BIS(2-BROMOETHYL)PHOSPHORODIAMIDIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
460 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 460 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 460 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/	DLT: stomatitis, hyperbilirubinemia... Dose limiting toxicities: stomatitis (grade 3, 1 pt) hyperbilirubinemia (grade 3, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/
480 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 480 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 480 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30279233/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30279233/	Sources: https://pubmed.ncbi.nlm.nih.gov/30279233/
550 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 550 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 550 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/	DLT: esophagitis... Dose limiting toxicities: esophagitis (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/
330 mg/m2 1 times / day multiple, intravenous MTD Dose: 330 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 330 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/	Other AEs: Diarrhea, Diarrhea... Other AEs: Diarrhea (all grades, 3 patients) Diarrhea (grade 3-4, 1 pt) Fatigue (all grades, 1 pt) Peripheral edema (all grades, 3 patients) Rash (all grades, 3 patients) Pneumonia (all grades, 6 patients) Pneumonia (grade 3-4, 6 patients) Nausea (all grades, 3 patients) Nausea (grade 3-4, 1 pt) Stomatitis (all grades, 6 patients) Stomatitis (grade 3-4, 4 patients) Dermatitis (all grades, 2 patients) Dermatitis (grade 3-4, 1 pt) Sepsis (all grades, 2 patients) Sepsis (grade 3-4, 2 patients) Hyperbilirubinemia (all grades, 2 patients) Hyperbilirubinemia (grade 3-4, 1 pt) Cough (all grades, 2 patients) Epistaxis (all grades, 2 patients) Multi-organ failure (all grades, 2 patients) Multi-organ failure (all grades, 2 patients) Neutropenic fever (grade 3-4, 2 patients) Multi-organ failure (grade 3-4, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/
340 mg/m2 1 times / day multiple, intravenous MTD Dose: 340 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 340 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30279233/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/30279233/	Other AEs: Anemia, Anemia... Other AEs: Anemia (all grades, 17 patients) Anemia (grade 3-4, 13 patients) Thrombocytopenia (all grades, 16 patients) Thrombocytopenia (grade 3-4, 11 patient) Neutropenia (all grades, 16 patients) Neutropenia (grade 3-4, 8 patients) Leukopenia (all grades, 13 patients) Leukopenia (grade 3-4, 6 patients) Nausea (all grades, 8 patients) Vomiting (all grades, 5 patients) Constipation (all grades, 4 patients) Diarrhea (all grades, 5 patients) Diarrhea (grade 3-4, 1 pt) Stomatitis (all grades, 6 patients) Stomatitis (grade 3-4, 2 patients) rash (all grades, 14 patients) Fatigue (all grades, 14 patients) Fatigue (grade 3-4, 2 patients) Edema (all grades, 4 patients) Infusion site reactions (all grades, 6 patients) Infusion site reactions (grade 3-4, 1 pt) Pyrexia (all grades, 5 patients) Hyperglycemia (all grades, 11 patient) Hyperglycemia (grade 3-4, 1 pt) Decreased appetite (all grades, 6 patients) Hypomagnesaemia (all grades, 5 patients) Peripheral neuropathy (all grades, 1 pt) Headache (all grades, 5 patients) Headache (grade 3-4, 1 pt) Dyspnea (all grades, 5 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/30279233/
460 mg/m2 1 times / day multiple, intravenous MTD Dose: 460 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 460 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/	Other AEs: Diarrhea, Diarrhea... Other AEs: Diarrhea (all grades, 17 patients) Diarrhea (grade 3-4, 2 patients) Fatigue (all grades, 9 patients) Fatigue (grade 3-4, 2 patients) Peripheral edema (all grades, 9 patients) Peripheral edema (grade 3-4, 1 pt) Rash (all grades, 9 patients) Pneumonia (all grades, 8 patients) Pneumonia (grade 3-4, 8 patients) Urinary tract infection (all grades, 8 patients) Dermatitis (grade 3-4, 6 patients) Nausea (all grades, 7 patients) Nausea (grade 3-4, 1 pt) Headache (all grades, 6 patients) Headache (grade 3-4, 2 patients) Stomatitis (all grades, 6 patients) Stomatitis (grade 3-4, 1 pt) Dermatitis (all grades, 2 patients) Sepsis (all grades, 3 patients) Sepsis (grade 3-4, 3 patients) Hyperbilirubinemia (all grades, 3 patients) Hyperbilirubinemia (grade 3-4, 2 patients) Cough (all grades, 2 patients) Epistaxis (all grades, 1 pt) Neutropenic fever (all grades, 17 patients) Neutropenic fever (grade 3-4, 17 patients) Thrombocytopenia (all grades, 2 patients) Thrombocytopenia (grade 3-4, 2 patients) Anemia (all grades, 3 patients) Anemia (grade 3-4, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/27169385/

AEs

PubMed

Title	Date	PubMed
Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer.	2015-05-01	25512461
Phase 1 study of the safety, tolerability, and pharmacokinetics of TH-302, a hypoxia-activated prodrug, in patients with advanced solid malignancies.	2011-05-01	21415214
Inhibition of both thioredoxin reductase and glutathione reductase may contribute to the anticancer mechanism of TH-302.	2010-09	19838642
Potent and highly selective hypoxia-activated achiral phosphoramidate mustards as anticancer drugs.	2008-04-24	18257544

Patents

Sample Use Guides

In Vivo Use Guide

The benefit of adding evofosfamide to doxorubicin as first-line therapy for advanced soft-tissue sarcomas was studied in international, open-label, randomised, phase 3, multicentre trial (TH CR-406/SARC021). This study was registered with ClinicalTrials.gov, number NCT01440088. Eligible patients were aged 15 years or older with a diagnosis of an advanced unresectable or metastatic soft-tissue sarcoma, of intermediate or high grade, for which no standard curative therapy was available, an Eastern Cooperative Oncology Group performance status of 0-1, and measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (1:1) to receive doxorubicin alone (75 mg/m2 via bolus injection administered over 5-20 min or continuous intravenous infusion for 6-96 h on day 1 of every 21-day cycle for up to six cycles) or doxorubicin (given via the same dose procedure) plus evofosfamide (300 mg/m2 intravenously for 30-60 min on days 1 and 8 of every 21-day cycle for up to six cycles).

Route of Administration: Intravenous

In Vitro Use Guide

TH-302 strongly inhibited the growth of both SCCVII and HT29 cells under hypoxia. The IC50 under hypoxia [IC50 (0.1% O2)] was 31.2±8.1 µM for SCCVII and 79.4±28.6 µM for HT29 cells, respectively. The IC50 under aerobic conditions [IC50 (21% O2)] was estimated to be >200 µM for both cell lines. These results suggest that TH-302 is significantly activated under hypoxic microenvironment to release the Br-IPM effecter moiety, thereby inhibiting cell growth.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:21:46 GMT 2025` Edited by `admin` on `Mon Mar 31 18:21:46 GMT 2025`
Record UNII	8A9RZ3HN8W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

evofosfamide [INN]

Preferred Name

English

EVOFOSFAMIDE

Official Name

English

(1-METHYL-2-NITRO-1H-IMIDAZOL-5-YL)METHYL N,N'-BIS(2-BROMOETHYL)DIAMIDOPHOSPHATE

Systematic Name

English

EVOFOSFAMIDE [JAN]

Common Name

English

(1-METHYL-2-NITRO-1H-IMIDAZOLE-5-YL)METHYL N,N'-BIS(2-BROMOETHYL) DIAMIDOPHOSPHATE

Common Name

English

TH-302

Code

English

PHOSPHORODIAMIDIC ACID, N,N'-BIS(2-BROMOETHYL)-, (1-METHYL-2-NITRO-1H-IMIDAZOL-5-YL)METHYL ESTER

Systematic Name

English

Evofosfamide [WHO-DD]

Common Name

English

EVOFOSFAMIDE [USAN]

Common Name

English

1-METHYL-2-NITRO-L H-IMIDAZOLE-5-YL) N,N-BIS(2-BROMOETHYL)DIAMIDOPHOSPHATE

Common Name

English

HAP-302

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C274