Evofosfamide

Summary

Evofosfamide (CHEMBL260046) is a phase-3 clinical-stage small-molecule antineoplastic agent; indicated across 8 conditions including metastatic melanoma and glioblastoma.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Indications: 8 conditions
• Clinical trials: 24
• Chemistry: 449.04 Da · C9H16Br2N5O4P

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL260046
Name	Evofosfamide
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11984561
ChEBI	CHEBI:231678
Molecular formula	C9H16Br2N5O4P
Molecular weight	449.04
InChIKey	UGJWRPJDTDGERK-UHFFFAOYSA-N

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

IUPAC name: 2-bromo-N-[(2-bromoethylamino)-[(3-methyl-2-nitroimidazol-4-yl)methoxy]phosphoryl]ethanamine

ChEBI definition: A member of the class of imidazoles that is 1H-imidazole substituted by methyl, nitro, and ({bis[(2-bromoethyl)amino]phosphoryl}oxy)methyl groups at positions 1, 2 and 5, respectively. It is a hypoxia-activated prodrug that targets hypoxic regions of tumors. The drug was being evaluated for first-line treatment of advanced pancreatic adenocarcinoma and advanced soft tissue sarcoma, in combination with chemotherapy (phase 3 trial now discontinued since the drug did not meet primary endpoints).

Pharmacological roles (ChEBI): antineoplastic agent, prodrug, alkylating agent.

Also known as: Evofosfamida, Evofosfamide, HAP-302, TH-302, EVOFOSFAMIDE, evofosfamide

Patent coverage: 261 distinct patent families (664 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Alpha-enolase.

Bioactivity

ChEMBL activities: 4 potent at pChembl ≥ 5 of 4 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ENO1	6.52	IC50	301	nM	CHEMBL_ACT_20677595
ENO1	6.05	IC50	897	nM	CHEMBL_ACT_20677598
ENO1	5.59	IC50	2554	nM	CHEMBL_ACT_20677586
ENO1	5.32	IC50	4838	nM	CHEMBL_ACT_20677589

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

8 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
metastatic melanoma	2	MONDO:0005191	EFO:0002617
glioblastoma	2	MONDO:0018177	EFO:0000519
soft tissue sarcoma	2	MONDO:0018078	EFO:1001968
neoplasm	1	MONDO:0005070	EFO:0000616
plasma cell myeloma	1	MONDO:0009693	EFO:0001378
exocrine pancreatic carcinoma	1	MONDO:0005192	EFO:0002618

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 24.

Phase distribution

Phase	Trials
PHASE1	10
PHASE2	8
PHASE1/PHASE2	4
PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01746979	PHASE3	COMPLETED	Clinical Trial Testing TH-302 in Combination With Gemcitabine in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma
NCT06782555	PHASE1/PHASE2	RECRUITING	A Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab
NCT06836726	PHASE2	NOT_YET_RECRUITING	Clinical Trial to Test Efficacy of Targeting Hypoxia Combined With ARSI After First-line ARSI Therapy for Castrate Resistant Prostate Cancer
NCT00742963	PHASE1/PHASE2	COMPLETED	Dose-Escalation Study of TH-302 in Combination With Doxorubicin to Treat Patients With Advanced Soft Tissue Sarcoma
NCT00743379	PHASE1/PHASE2	COMPLETED	Dose-Escalation Study of TH-302 in Combination With A) Gemcitabine or B) Docetaxel or C) Pemetrexed to Treat Advanced Solid Tumors
NCT01144455	PHASE2	COMPLETED	Study of the Safety and Efficacy of TH-302 in Combination With Gemcitabine Compared With Gemcitabine Alone in Previously Untreated Patients With Pancreatic Adenocarcinoma
NCT01403610	PHASE2	COMPLETED	Safety and Efficacy Study of TH-302 CNS Penetration in Recurrent High Grade Astrocytoma Following Bevacizumab
NCT01522872	PHASE1/PHASE2	UNKNOWN	Open-label Study of TH-302 and Dexamethasone With or Without Bortezomib or Pomalidomide in Subjects With Relapsed/Refractory Multiple Myeloma
NCT01864538	PHASE2	TERMINATED	A Phase 2 Biomarker - Enriched Study of TH-302 in Subjects With Advanced Melanoma
NCT02255110	PHASE2	TERMINATED	A Japanese Trial of TH-302 in Subjects With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma
NCT02342379	PHASE2	COMPLETED	TH-302 in Combination With Bevacizumab for Glioblastoma
NCT02402062	PHASE2	COMPLETED	A Study to Assess the Safety and the Efficacy of the Combination of TH-302 and Sunitinib in Neuroendocrine Pancreatic Tumours
NCT02433639	PHASE2	COMPLETED	Study of TH-302 Monotherapy as Second-line Treatment in Advanced Biliary Tract Cancer
NCT00495144	PHASE1	COMPLETED	A Phase I Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of TH-302 in Patients With Advanced Solid Tumors
NCT01149915	PHASE1	COMPLETED	Study of Hypoxia-Activated Prodrug TH-302 to Treat Advanced Leukemias
NCT01381822	PHASE1	UNKNOWN	Dose-Escalation Study of TH-302 in Combination With Sunitinib to Treat Patients With Advanced Renal Cell Carcinoma,Gastrointestinal Stromal Tumors and Pancreatic Neuroendocrine Tumors
NCT01485042	PHASE1	COMPLETED	Dose Escalation Study of Pazopanib Plus TH-302
NCT01833546	PHASE1	COMPLETED	A Japanese Phase 1 Trial of TH-302 in Subjects With Solid Tumors and Pancreatic Cancer
NCT02020226	PHASE1	UNKNOWN	A Cardiac Safety Study of TH-302 in Patients With Advanced Solid Tumors
NCT02047500	PHASE1	TERMINATED	Phase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer
NCT02076230	PHASE1	COMPLETED	A Phase 1 TH-302 Mass Balance Trial
NCT02598687	PHASE1	WITHDRAWN	Testing TH-302, in Combination With Preoperative Chemoradiotherapy, in Esophageal Cancer.
NCT03098160	PHASE1	UNKNOWN	Immunotherapy Study of Evofosfamide in Combination With Ipilimumab
NCT02712567	Not specified	NO_LONGER_AVAILABLE	SARC021C: A Continuation Study of TH-CR-406/SARC021

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).