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Evofosfamide was the most advanced hypoxia-activated drug, designed to kill the oxygen-starved tumour cells radiotherapy and chemotherapy miss, but it failed both of its phase 3 trials in 2015.
Evofosfamide (TH-302), developed by Threshold Pharmaceuticals with Merck KGaA, showed promising responses in early trials. In 2015 both phase 3 trials missed their overall survival endpoints: MAESTRO with gemcitabine in pancreatic cancer and TH CR-406 with doxorubicin in soft-tissue sarcoma. Development largely stopped, though small studies with radiotherapy and immunotherapy continue, and the programme remains the reference case for why hypoxia targeting is hard: patients were not selected for hypoxia, and the drug's activation depends on oxygen levels that vary from hour to hour.
A nitroimidazole-linked prodrug that is inert in oxygenated tissue and releases the DNA-crosslinking agent bromo-isophosphoramide mustard only in the low-oxygen regions of tumours.
1.Evofosfamide slips into a pocket on its target.
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Query for this drug: (TITLE:"Evofosfamide" OR ABSTRACT:"Evofosfamide" OR TITLE:"TH-302" OR ABSTRACT:"TH-302") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Evofosfamide, not a curated reading list.
Shares Tumour hypoxia: imaging and modification and the tag radiation-wave3.
Shares Sarcomas (soft tissue, bone, GIST) and the tag radiation-wave3.
Shares Sarcomas (soft tissue, bone, GIST) and the tag radiation-wave3.
Shares A Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab, Pancreatic ductal adenocarcinoma.
Shares Threshold Pharmaceuticals, Sarcomas (soft tissue, bone, GIST), Pancreatic ductal adenocarcinoma.
Shares Tumour hypoxia: imaging and modification, Sarcomas (soft tissue, bone, GIST).