Phase I Study of AT13148, a Novel AGC Kinase Inhibitor

Inclusion Criteria: 1. Histologically proven advanced solid tumours, refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient. Paraffin-embedded tumour tissue must be available for genetic mutation status testing. 2. Life expectancy of at least 12 weeks 3. World Health Organisation (WHO) performance status of 0, 1 or 2 4. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within 7 days before their first dose of AT13148 taken between Day -7 to -4. Laboratory Test Value required Haemoglobin (Hb) ≥ 9.0 g/dL Absolute neutrophil count ≥ 1.5 x 10\^9 /L Platelet count ≥ 100 x 10\^9/L Fasting glucose ≤ 7 mmol/L Either: Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) Or: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x (ULN) unless raised due to tumour in which case up to 5 x ULN is permissible Either: Calculated creatinine clearance ≥ 50 mL/min Or: Isotope clearance measurement ≥ 50mL/min (uncorrected) 5. Adequate lung function indicated by a resting oxygen saturation level (on air) ≥ 94%, a CO-transfer factor \> 60% 6. 18 years or over 7. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up Exclusion Criteria: 1. Radiotherapy (except for palliative reasons), endocrine therapy (except luteinizing hormone releasing hormone (LHRH) agonists for prostate cancer), immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C) and 4 weeks for investigational medicinal products) before treatment. 2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient. 3. Symptomatic brain metastases (if present they must have been stable for \> 3 months). 4. Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) during the study and for six months afterwards are considered eligible. 5. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception \[condom plus spermicide\] during the study and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate. 6. Major thoracic or abdominal surgery from which the patient has not yet recovered. 7. At high medical risk because of non-malignant systemic disease including active uncontrolled infection. 8. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV). 9. History of auto-immune disease or known allergy to peanuts. 10. Concurrent hypotension defined as a baseline supine blood pressure (BP) systolic \< 90 mmHg. 11. Patients receiving anti-hypertensive treatment or treatment with beta- blockers or rate-limiting calcium agents. A washout period of 5 x half- life of the drug should be applied following withdrawal of any of these treatments. 12. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association \[NYHA\]), prior history of cardiac ischaemia or prior history of cardiac arrhythmia. Coronary angioplasty or stenting in the previous 12 months. 13. Patients with a known left ventricular ejection fraction (LVEF) \< 50%. A multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) must be performed in all patients. 14. Concurrent diabetes requiring treatment (diet-controlled diabetes would be acceptable). 15. Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within eight weeks. 16. A history of or underlying interstitial lung disease. 17. Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical study. 18. Is a participant or plans to participate in another interventional clinical study whilst taking part in this study. Participation in an observational study would be acceptable.