Threshold Pharmaceuticals initiating phase 2 study of advanced melanoma drug

Threshold Pharmaceuticals has announced it is initiating a phase 2 clinical trial to evaluate the efficacy and safety of its investigational hypoxia-targeted drug in treating patients with advanced melanoma.

The study of TH-302, designed for activation under tumor hypoxic conditions, also will investigate biomarkers including serum, tumor biopsy and PET imaging biomarkers that could predict treatment outcomes associated with tumor response to the therapy, according to a press release. Threshold’s partner in the venture, Merck KGaA, will fund 70% of the study’s development costs.

“Hypoxia is believed to be an important therapeutic target for patients with metastatic melanoma,” principal investigator Anthony Joshua, MBBS, PhD, FRACP, medical oncologist at Princess Margaret Cancer Centre and assistant professor at the University of Toronto, said in the release. “Targeting hypoxic melanoma cells may help in slowing tumor progression and treatment resistance and has the potential to be an adjunct to current therapies.”

The multicenter trial will investigate T-302 administered in up to 40 patients with advanced melanoma at 480 mg/m2 weekly on a 28-day cycle of 3 weeks on, 1 week off. Three-month progression-free survival will be the primary endpoint. Response rate and duration, overall survival, safety and evaluation of potential imaging, serum and tissue biomarkers that may be associated with tumor response and predict efficacy and safety are among the secondary endpoints.

Responses were observed in 56% of patients (n=34) with advanced melanoma treated with TH-302 in a previous phase 1 trial, according to the release.

TH-302 also is being investigated in two phase 3 trials, including one in combination with doxorubicin vs. doxorubicin monotherapy in patients with soft tissue sarcoma and another in combination with gemcitabine vs. gemcitabine and placebo in patients with advanced pancreatic cancer, the release said. Both trials have been granted Special Protocol Agreements by the FDA.