Evofosfamide (INN,[1] USAN;[2] formerly known as TH-302) is a compound being evaluated in clinical trials for the treatment of multiple tumor types as a monotherapy and in combination with chemotherapeutic agents and other targeted cancer drugs.

This compound has been evaluated in the treatment of solid tumors, as a hypoxia-activated prodrug (HAPs), such chemical agents in low oxygen conditions undergo bio-reduction to yield cancer fighting cytotoxic breakdown products.

This investigational therapeutic approach of targeting the cytotoxin to hypoxic zones in tumors may cause less broad systemic toxicity that is seen with untargeted cytotoxic chemotherapies.

Subsequent structure-activity relationship (SAR) studies showed that replacement of the chlorines in the alkylator portion of the prodrug with bromines improved potency about 10-fold.

Here’s a simplified overview of the process: This synthesis method allows Evofosfamide to target hypoxic tumor cells selectively, making it a promising candidate in cancer therapy.

[15] Evofosfamide (TH-302) is currently being evaluated in clinical studies as a monotherapy and in combination with chemotherapy agents and other targeted cancer drugs.

The indirect comparison of both studies shows comparable hematologic toxicity and efficacy profiles of evofosfamide and ifosfamide in combination with doxorubicin.

However, in the Phase 3 TH-CR-406/SARC021 study (conducted in collaboration with the Sarcoma Alliance for Research through Collaboration (SARC)), patients with locally advanced unresectable or metastatic soft tissue sarcoma treated with evofosfamide in combination with doxorubicin did not demonstrate a statistically significant improvement in OS compared with doxorubicin alone (HR: 1.06; 95% CI: 0.88 - 1.29).

[citation needed] Both, evofosfamide and protein-bound paclitaxel (nab-paclitaxel) have been investigated in combination with gemcitabine in patients with metastatic pancreatic cancer.

In the Phase 3 MAESTRO study, patients with previously untreated, locally advanced unresectable or metastatic pancreatic adenocarcinoma treated with evofosfamide in combination with gemcitabine did not demonstrate a statistically significant improvement in overall survival (OS) compared with gemcitabine plus placebo (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.71 - 1.01; p=0.0589).

[citation needed] Schedule B: On days 1, 8 and 15 every 4 weeks (1) statistically not significant Oxygen deficient conditions are linked to tumor progression throughout the body and poses an issue in cancer treatments such as chemotherapy and radiation.

[49] These findings allow for evidence for Evofosfamide to be pushed towards clinical trials to further investigate the potential to be developed as an FDA approved anticancer drug.

Any inability of the third-party contract manufacturers to produce adequate quantities could adversely affect the clinical development and commercialization of evofosfamide.