Ensayos clínicos

Inclusion Criteria

• Histologically proven advanced malignant pleural mesothelioma, advanced peritoneal mesothelioma (for dose escalation cohort only), non-squamous non-small cell lung cancer (NSCLC) (stage IIIB/IV) or metastatic uveal melanoma or advanced  liver cell cancer or recurrent high-grade glioma
• Subjects with mesothelioma or NSCLC or uveal melanoma must be chemotherapy naïve except for those EGFR mutant or ALK positive must have had an EGFR tyrosine kinase inhibitor or ALK inhibitor (if available)
• Subjects with HCC must have already failed sorafenib (due to progressive disease and/or side effects)
• Subjects with glioma must have already failed radiotherapy ± temozolomide (due to progressive disease and/or side effects)
• ASS1 deficiency using immunohistochemistry demonstrated on tissue specimen (cytospin specimen are acceptable)
•  ECOG PS 0-1
• Expected survival of at least 3 months 
• Age 18 years or over (there is no upper age limit) 
• Evaluable disease by modified RECIST criteria for MPM and RECIST 1.1 criteria for peritoneal mesothelioma, non-squamous NSCLC, uveal melanoma, HCC and glioma 
• Written (signed and dated) informed consent and must be capable of co-operating with treatment and follow up 
• Adequate hematologic, hepatic, and renal function

Exclusion Criteria

• Radiotherapy (except for palliative reasons), targeted therapy, or immunotherapy (except for uveal melanoma) the previous four weeks before study treatment
• Ongoing toxic manifestations of previous treatments
• Symptomatic brain or spinal cord metastases (patients must be stable for > 3 months post radiotherapy or surgery) for subjects with mesothelioma, NSCLC, uveal melanoma (excludes subjects with HCC or glioma)
• Major thoracic or abdominal surgery from which the patient has not yet recovered
• Serious infection requiring treatment with intravenous antibiotics at the time of study entrance, or an infection requiring intravenous therapy within 7 days prior to the first dose of study treatment