The first patient has been dosed in a Phase 1 clinical trial evaluating the immunotherapy combination of Threshold Pharmaceuticals‘ evofosfamide (TH-302) plus Bristol-Myers Squibb‘s Yervoy (ipilimumab) for the treatment of patients with advanced solid malignancies.
The single-arm, open-label Phase 1 trial (NCT03098160), being conducted at the University of Texas MD Anderson Cancer Center in Houston, will enroll up to 69 patients with confirmed metastatic or locally advanced prostate cancer, metastatic pancreatic cancer, melanoma, or human papillomavirus (HPV) negative squamous cell carcinoma of the head and neck.
Eligible participants are those who have failed to respond to standard therapy, progressed despite standard therapy, or those for whom standard therapy does not offer the potential for increased survival.
All patients who meet the study criteria will receive evofosfamide on days one and eight of the first two cycles and Yervoy on day eight of a 28-day cycle. The primary objective of the study is to determine the recommended dose of the combo therapy to be used in a Phase 2 study. Secondary objectives include duration of response, progression-free survival, overall survival, safety, tolerability, and pharmacokinetics (how the drug is processed in the body).
Evofosfamide is an investigational hypoxia-activated prodrug that is in clinical development for cancer treatment. The prodrug is activated only at very low levels of oxygen (hypoxia). Such levels are common in human solid tumors because tumor cells are metabolically active and consume high rates of oxygen.
In preclinical studies, evofosfamide has sensitized highly resistant solid tumor models to treatment with certain immune checkpoint inhibitors by disrupting hypoxic zones.
Hypoxia in tumors forms a barrier to T-cells and promotes the resistance of immunotherapy treatments in solid tumors.
“We believe that adding evofosfamide to certain immunotherapies has the potential to render some of the most therapeutically resistant cancers more sensitive to the immunotherapy, and we are excited to have dosed the first patient in this study,” Tillman Pearce, MD, chief medical officer at Threshold Pharmaceuticals, said in a press release.
Pearce thanked MD Anderson’s Michael Curran, PhD, for his preclinical research that led to the knowledge that “certain tumors have hypoxic zones that resist infiltration by T-cells, which are capable of attacking and killing tumor cells,” and that a combo therapy of evofosfamide and anti-PD-1 or anti-CTLA-4 treatment “opens up the hypoxic zones to T-cell infiltration.”