A Phase 2 Biomarker – Enriched Study of TH-302 in Subjects With Advanced Melanoma

Inclusion Criteria:

At least 18 years of age
Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's Regional Ethics Board/Independent Ethics Committee (REB/IEC)
Histologically documented cutaneous or mucosal malignant melanoma, which is recurrent or metastatic and is not curable by surgical or other means.
Adequate tumour tissue (greater than 0.5cm3 preferred, 3 X core biopsy acceptable) available and agreement from subjects that this tissue from their primary and/or metastatic tumour be made available for assessment of potential biomarkers.
Ability and availability to complete all prescribed biomarker studies (Screening and after Cycle 2).
Recovered to Grade 1 from reversible toxicities of prior therapy
Presence of clinically and/or radiologically documented disease. At least one site of disease (which will not be removed during the course of the study) must be uni-dimensionally measurable as per RECIST 1.1 or clinically quantifiable (such as in the case of skin disease)
ECOG performance status of 0 - 1.
Prior treatment with any number of immunotherapies (e.g., IL2, ipilimumab), targeted therapies (e.g., vemurafenib) are permitted but no more than one 1 prior chemotherapy
Acceptable liver function
Acceptable renal function
Acceptable hematologic status (without growth factor support for neutropenia or transfusion dependency):
Normal 12-lead ECG (clinically insignificant abnormalities permitted)
Female subjects of childbearing age must have a negative urine HCG test unless prior hysterectomy or menopause (defined as age above 55 and twelve months without menstrual activity). Female subjects should not become pregnant or breast-feed while on this study. Sexually active male and female subjects should use effective birth control.

Exclusion Criteria:

Anticancer treatment with radiation therapy, targeted therapies, chemotherapy, immunotherapy, hormones or other antitumour therapies within 28 days prior to first dose of TH-302.
Subjects who have received any other investigational drug or agent within 28 days of first dose of TH-302
Current use of drugs with known cardiotoxicity
Significant cardiac dysfunction:
Seizure disorders requiring anticonvulsant therapy
Progressing brain metastases (unless previously treated and stable disease for a period of greater than or equal to 3 months on repeat MRI following definitive treatment).
History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for greater than 2 years
Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation less than 90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause hypoxia of normal tissue.
Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1, without complete recovery
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
Prior therapy with an hypoxic cytotoxin
Known infection with HIV or active infection with hepatitis B or hepatitis C
History of allergic reaction to a structural compound or biological agent similar to TH-302
Pregnancy or breast-feeding
Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
Unwillingness or inability to comply with the study protocol for any reason.