US-based biopharmaceutical firm Threshold Pharmaceuticals has begun dosing patients in a Phase I clinical trial of evofosfamide in combination with ipilimumab to treat various cancers.
The trial will include patients with metastatic or locally advanced prostate cancer, metastatic pancreatic cancer, melanoma or human papillomavirus (HPV) negative squamous cell carcinoma of head and neck in case conventional treatment does not provide the potential for increased survival.
Threshold’s evofosfamide is an investigational, hypoxia-activated prodrug of a bis-alkylating agent that is selectively triggered under severe hypoxic tumour conditions found in multiple solid tumours.
Ipilimumab is a monoclonal antibody developed to induce the immune system by targeting a CTLA-4 protein receptor that downregulates the system.
Designed to enrol approximately 69 patients, the single-arm, open-label Phase I trial will administer evofosfamide on day one and eight of the first two cycles, while ipilimumab will be given on day eight of a 28-day cycle.
Threshold Pharmaceuticals chief medical officer Tillman Pearce said: "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.
"Thanks to preclinical research conducted by Dr Curran at MD Anderson Cancer Centre, it is well-understood that certain tumours have hypoxic zones that resist infiltration by T-cells, which are capable of attacking and killing tumour cells, and that combination therapy with evofosfamide and anti-CTLA-4 / anti-PD-1 treatment opens up the hypoxic zones to T-cell infiltration."
The trial’s primary endpoint is immune-related response evaluation criteria in solid tumours (irRECIST) response rate, while secondary endpoints include safety, tolerability, duration of response, pharmacokinetics, progression-free survival and overall survival.