{"entity":{"id":"evofosfamide","kind":"drug","name":"Evofosfamide","aka":[],"tldr":"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.","summary":"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.","status":"negative","asOf":"2026-09-16","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Evofosfamide"}],"tags":["radiation-wave3"],"related":[],"cancers":["pancreatic","sarcoma"],"sections":[],"technologies":["tumour-hypoxia-modification"],"targets":[],"drugs":[],"companies":["threshold-pharmaceuticals"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"notes":[],"provenance":{"editedBy":"OnCo radiation expansion","editedOn":"2026-09-16"},"code":"TH-302","modality":"Hypoxia-activated prodrug (small molecule alkylating agent)","mechanism":"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.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/evofosfamide/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"technology":[{"id":"tumour-hypoxia-modification","kind":"technology","name":"Tumour hypoxia: imaging and modification","route":"/technologies/tumour-hypoxia-modification/"}],"company":[{"id":"threshold-pharmaceuticals","kind":"company","name":"Threshold Pharmaceuticals","route":"/companies/threshold-pharmaceuticals/"}]}}