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Merck Walks Away From Cancer Drug Evofosfamide

Company disappointed by late-stage results

Merck has announced that it is not planning to file for approval of evofosfamide in advanced soft-tissue sarcoma and advanced pancreatic adenocarcinoma. The decision was made in light of disappointing results from two phase III studies of evofosfamide in combination with chemotherapy in these two types of cancer. The findings were reported by Threshold Pharmaceuticals Inc., which has a global license and co-development agreement for evofosfamide with Merck.

Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe tumor hypoxic conditions –– a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood-vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic.

The MAESTRO (MetAstatic or UnrESectable PancreaTic AdenocaRcinOma) trial was a randomized, placebo-controlled, international, double-blind study designed to assess the efficacy and safety of evofosfamide (340 mg/m2) in combination with gemcitabine (1,000 mg/m2), compared with gemcitabine and placebo, in 693 patients with previously untreated, locally advanced, unresectable or metastatic pancreatic adenocarcinoma. The trial’s primary endpoint was overall survival (OS).

In this study, patients treated with evofosfamide plus gemcitabine did not demonstrate a statistically significant improvement in OS compared with those given gemcitabine plus placebo (hazard ratio [HR], 0.84; P = 0.0589).

The TH-CR-406/SARC021 trial was a randomized, open-label global study designed to assess the efficacy and safety of evofosfamide (300 mg/m2) in combination with doxorubicin (75 mg/m2) compared with doxorubicin alone in 640 patients with locally advanced unresectable or metastatic soft-tissue sarcoma previously untreated with chemotherapy. The trial’s primary endpoint was OS.

Patients treated with evofosfamide in combination with doxorubicin did not demonstrate a statistically significant improvement in OS compared with doxorubicin alone (HR, 1.06).

Merck’s pharmaceutical pipeline remains focused on oncology, immuno-oncology, and immunology products, the company says. In immuno-oncology, Merck, together with Pfizer, is researching avelumab, an investigational anti-programmed death ligand-1 (PD-L1) antibody, in more than 15 tumor types.

Sources: BioSpace; December 7, 2015; and Threshold Pharmaceuticals; December 7, 2015.

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