The developer of evofosfamide announced that two phase III trials of the agent in advanced soft-tissue sarcoma and in advanced pancreatic cancer did not meet their primary endpoints.
The developer of evofosfamide announced that two phase III trials of the agent in advanced soft-tissue sarcoma and in advanced pancreatic cancer did not meet their primary endpoints. The drug failed to improve overall survival (OS) in either of the two trials.
Evofosfamide (Threshold Pharmaceuticals with Merck) is a hypoxia-activated prodrug. It is activated under severe hypoxic conditions, which is a feature of many solid tumors due to insufficient blood supply; bone marrow of patients with hematologic malignancies can also be severely hypoxic.
The phase III TH-CR-406/SARC021 trial compared evofosfamide in combination with doxorubicin to doxorubicin alone. It included a total of 640 patients randomized to those two study arms; all included patients had locally advanced unresectable or metastatic soft-tissue sarcoma, and all were previously untreated with chemotherapy.
Evofosfamide failed to improve OS in the study, which was the primary endpoint. The study drug along with doxorubicin yielded a hazard ratio for survival of 1.06 (95% confidence interval [CI], 0.88–1.29). As a result, the company announced it will not be pursuing further development of evofosfamide in this malignancy. Secondary endpoints, including progression-free survival, response rate, safety, and pharmacokinetics will be reported at a later date.
Similarly, the MAESTRO phase III trial also did not show benefit with the drug. That study included 693 patients with previously untreated, locally advanced, unresectable or metastatic pancreatic adenocarcinoma randomized to gemcitabine with either evofosfamide or placebo. The evofosfamide regimen had a hazard ratio for OS of 0.84 (95% CI, 0.71–1.01; P = .0589). Again, the company has ceased development of evofosfamide for use in pancreatic cancer.
“We are surprised and disappointed that these studies did not show that evofosfamide could extend the lives of patients with these two difficult-to-treat diseases,” said Barry Selick, PhD, the CEO of Threshold Pharmaceuticals, in a press release. “While we believe there remains substantial data to support the role of hypoxia in cancer treatment resistance, we are deeply frustrated with our inability in these trials to impact that in a meaningful way.”
Evofosfamide is being studied in several other ongoing trials, including a Japanese trial of soft-tissue sarcoma as well as others in lung cancer, myeloma, and other malignancies.